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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis
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作者 Yifei Wang Yidan Ma +14 位作者 Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2024年第3期282-297,共16页
Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not ... Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients. 展开更多
关键词 Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment PROGNOSIS
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Low testing rates and high BRCA prevalence: Poly (ADP-ribose) polymerase inhibitor use in Middle East BRCA/homologous recombination deficiency-positive cancer patients
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作者 Naveed Syed Ashish Vittalrao Chintakuntlawar +6 位作者 Deepti Vilasini Aisha Mohamed Al Salami Riad Al Hasan Imrana Afrooz Kanishka Uttam Chandani Ashok Uttam Chandani Aref Chehal 《World Journal of Clinical Oncology》 2024年第7期848-858,共11页
BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breas... BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients. 展开更多
关键词 homologous recombination repair BRCA1 BRCA2 homologous recombination deficiency Ovarian cancer Breast cancer Poly(ADP-ribose)polymerase inhibitors OLAPARIB DNA double-strand breaks
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Establishing the homologous recombination score threshold in metastatic prostate cancer patients to predict the efficacy of PARP inhibitors
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作者 Diwei Zhao Anqi Wang +8 位作者 Yuanwei Li Xinyang Cai Junliang Zhao Tianyou Zhang Yi Zhao Yu Dong Fangjian Zhou Yonghong Li Jun Wang 《Journal of the National Cancer Center》 2024年第3期280-287,共8页
Background:The homologous recombination deficiency(HRD)score serves as a promising biomarker to iden-tify patients who are eligible for treatment with PARP inhibitors(PARPi).Previous studies have suggested a 3-biomark... Background:The homologous recombination deficiency(HRD)score serves as a promising biomarker to iden-tify patients who are eligible for treatment with PARP inhibitors(PARPi).Previous studies have suggested a 3-biomarker Genomic Instability Score(GIS)threshold of≥42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer.However,the GIS threshold for prostate cancer(PCa)is still lacking.Here,we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients.Methods:A total of 181 patients with metastatic castration-resistant PCa were included in this study.Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair(HRR)genes and copy number variation(CNV)analysis.The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms(SNP)distributed across the human genome,incorporating three SNP-based as-says:loss of heterozygosity,telomeric allelic imbalance,and large-scale state transition.The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors.The relation-ship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed.Results:Genomic testing was succeeded in 162 patients.In our cohort,61 patients(37.7%)had HRR mutations(HRRm).BRCA mutations occurred in 15 patients(9.3%).The median HRD score was 4(ranged from 0 to 57)in the total cohort,which is much lower than that in breast and ovarian cancers.Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores.CNV occured more frequently in patients with HRRm.The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores≥43.In the 16 patients who received PARPi in our cohort,4 patients with a high HRD score achieved an objective response rate(ORR)of 100%while 12 patients with a low HRD score achieved an ORR of 8.3%.Progression-free survival(PFS)in HRD high patients was longer compared to HRD low patients,regardless of HRRm.Conclusions:A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study.Future studies are needed to further verify this threshold. 展开更多
关键词 homologous recombination deficiency score THRESHOLD PARP inhibitors homologous recombination repair pathway MUTATION BRCA
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The evolutionarily diverged single-stranded DNA-binding proteins SSB1/SSB2 differentially affect the replication,recombination and mutation of organellar genomes in Arabidopsis thaliana
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作者 Weidong Zhu Jie Qian +6 位作者 Yingke Hou Luke R.Tembrock Liyun Nie Yi-Feng Hsu Yong Xiang Yi Zou Zhiqiang Wu 《Plant Diversity》 2025年第1期127-135,共9页
Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(... Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes. 展开更多
关键词 SSB Organellar genomes REPLICATION recombination MUTATION
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Homologous recombination in DNA repair and DNA damage tolerance 被引量:30
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作者 Xuan Li Wolf-Dietrich Heyer 《Cell Research》 SCIE CAS CSCD 2008年第1期99-113,共15页
Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs). In addition, recombination provides c... Homologous recombination (HR) comprises a series of interrelated pathways that function in the repair of DNA double-stranded breaks (DSBs) and interstrand crosslinks (ICLs). In addition, recombination provides critical support for DNA replication in the recovery of stalled or broken replication forks, contributing to tolerance of DNA damage. A central core of proteins, most critically the RecA homolog Rad51, catalyzes the key reactions that typify HR: homology search and DNA strand invasion. The diverse functions of recombination are reflected in the need for context-specific factors that perform supplemental functions in conjunction with the core proteins. The inability to properly repair complex DNA damage and resolve DNA replication stress leads to genomic instability and contributes to cancer etiology. Mutations in the BRCA2 recombination gene cause predisposition to breast and ovarian cancer as well as Fanconi anemia, a cancer predisposition syndrome characterized by a defect in the repair of DNA interstrand crosslinks. The cellular functions of recombination are also germane to DNA-based treatment modalities of cancer, which target replicating cells by the direct or indirect induction of DNA lesions that are substrates for recombination pathways. This review focuses on mechanistic aspects of HR relating to DSB and ICL repair as well as replication fork support. 展开更多
关键词 DNA repair double-strand breaks genome stability homologous recombination interstrand crosslinks stalled replication forks
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Construction of recombinant industrial Saccharomyces cerevisiae strain with bglS gene insertion into PEP4 locus by homologous recombination 被引量:6
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作者 Qiang ZHANG Qi-he CHEN Ming-liang FU Jin-ling WANG Hong-bo ZHANG Guo-qing HE 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第7期527-535,共9页
The bglS gene encoding endo-1,3-1,4-β-glucanase from Bacillus subtil& was cloned and sequenced in this study. The bglS expression cassette, including PGK1 promoter, bglS gene fused to the signal sequence of the yeas... The bglS gene encoding endo-1,3-1,4-β-glucanase from Bacillus subtil& was cloned and sequenced in this study. The bglS expression cassette, including PGK1 promoter, bglS gene fused to the signal sequence of the yeast mating pheromone a-factor (MFals), and ADH1 terminator with G418-resistance as the selected marker, was constructed. Then one of the PEP4 allele of Saccharomyces cerevisiae WZ65 strain was replaced by bglS expression cassette using chromosomal integration of polymerase chain reaction (PCR)-mediated homologous recombination, and the bglS gene was expressed simultaneously. The recombinant strain S. cerevisiae (SC-βG) was preliminarily screened by the clearing hydrolysis zone formed after the barley β-glucan was hydrolyzed in the plate and no proteinase A (PrA) activity was measured in fermenting liquor. The results of PCR analysis of genome DNA showed that one of the PEP4 allele had been replaced and bglS gene had been inserted into the locus of PEP4 gene in recombinant strains. Different endo-1,3-1,4-β-glucanase assay methods showed that the recombinant strain SC-βG had high endo-1,3-1,4-β-glucanase expression level with the maximum of 69.3 U/(h·ml) after 60 h of incubation. Meanwhile, the Congo Red method was suitable for the determination of endo-1,3-1,4-β-glucanase activity during the actual brewing process. The current research implies that the constructed yeast strain could be utilized to improve the industrial brewing property of beer. 展开更多
关键词 Endo-1 3-1 4-β-glucanase (bglS) Gene replacement homologous recombination Bacillus subtilis PEP4 gene Saccharomyces cerevisiae
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The mutational pattern of homologous recombination(HR)-associated genes and its relevance to the immunotherapeutic response in gastric cancer 被引量:6
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作者 Yue Fan Haifeng Ying +7 位作者 Xueying Wu Huan Chen Ying Hu Henghui Zhang Lijia Wu Ying Yang Beibei Mao Lan Zheng 《Cancer Biology & Medicine》 SCIE CAS CSCD 2020年第4期1002-1013,共12页
Objective:Currently,there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors(ICIs)for patients with gastric cancer(GC).Homologous recombination deficienc... Objective:Currently,there is an urgent need to identify immunotherapeutic biomarkers to increase the benefit of immune checkpoint inhibitors(ICIs)for patients with gastric cancer(GC).Homologous recombination deficiency(HRD)can modify the tumor immune microenvironment by increasing the presence of tumor-infiltrating lymphocytes and therefore might serve as a biomarker of immunotherapeutic response.We aimed to analyze the mutational pattern of HR-associated genes in Chinese patients with GC and its relevance to the tumor immune profile and clinical immunotherapeutic response.Methods:A panel of 543 cancer-associated genes was used to analyze genomic profiles in a cohort comprising 484 Chinese patients with GC.Correlations between HR gene mutations and tumor immunity or clinical outcomes were identified via bioinformatic analysis using 2 GC genomic datasets(TCGA and MSK-IMPACT).Results:Fifty-one of the 484(10.54%)patients carried at least one somatic mutation in an HR gene;ATM(16/484,3.31%)was among the most frequently mutated HR genes in the Chinese cohort.Mutations in HR genes were associated with elevated tumor mutational burden,enhanced immune activity,and microsatellite instability status.In the MSK-IMPACT cohort comprising 49 patients with stomach adenocarcinoma or gastroesophageal junction adenocarcinoma treated with ICIs,patients with HR-mut GC(n=12)had significantly better overall survival than those with HR-wt GC(n=37)(log-rank test,P<0.05).Conclusions:Our data suggest that detection of somatic mutations in HR genes might aid in identifying patients who might benefit from immune checkpoint blockade therapy. 展开更多
关键词 Gastric cancer homologous recombination deficiency IMMUNOTHERAPY BIOMARKER
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BLM helicase inhibition synergizes with PARP inhibition to improve the radiosensitivity of olaparib resistant non-small cell lung cancer cells by inhibiting homologous recombination repair 被引量:2
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作者 Yangyang Kong Chang Xu +11 位作者 Xiaohui Sun Hao Sun Xiaotong Zhao Ningning He Kaihua Ji Qin Wang Liqing Du Jinhan Wang Manman Zhang Yang Liu Yan Wang Qiang Liu 《Cancer Biology & Medicine》 SCIE CAS CSCD 2022年第8期1150-1171,共22页
Objective:We aimed to investigate the radiosensitizing efficacy of the poly-ADP-ribose polymerase(PARP)inhibitor,olaparib,and the Bloom syndrome protein(BLM)helicase inhibitor,ML216,in non-small cell lung cancer(NSCLC... Objective:We aimed to investigate the radiosensitizing efficacy of the poly-ADP-ribose polymerase(PARP)inhibitor,olaparib,and the Bloom syndrome protein(BLM)helicase inhibitor,ML216,in non-small cell lung cancer(NSCLC)cells.Methods:Radiosensitization of NSCLC cells was assessed by colony formation and tumor growth assays.Mechanistically,the effects of ML216,olaparib,and radiation on cell and tumor proliferation,DNA damage,cell cycle,apoptosis,homologous recombination(HR)repair,and non-homologous end joining(NHEJ)repair activity were determined.Results:Both olaparib and ML216 enhanced the radiosensitivities of olaparib-sensitive H460 and H1299 cells,which was seen as decreased surviving fractions and Rad51 foci,increased total DNA damage,andγH2AX and 53BP1 foci(P<0.05).The expressions of HR repair proteins were remarkably decreased in olaparib-treated H460 and H1299 cells after irradiation(P<0.05),while olaparib combined with ML216 exerted a synergistic radiosensitization effect on olaparib-resistant A549 cells.In addition to increases of double strand break(DSB)damage and decreases of Rad51 foci,olaparib combined with ML216 also increased pDNA-PKcs(S2056)foci,abrogated G2 cell cycle arrest,and induced apoptosis in A549 lung cancer after irradiation in vitro and in vivo(P<0.05).Moreover,Western blot showed that olaparib combined with ML216 and irradiation inhibited HR repair,promoted NHEJ repair,and inactivated cell cycle checkpoint signals both in vitro and in vivo(P<0.05).Conclusions:Taken together,these results showed the efficacy of PARP and BLM helicase inhibitors for radiosensitizing NSCLC cells,and supported the model that BLM inhibition sensitizes cells to PARP inhibitor-mediated radiosensitization,as well as providing the basis for the potential clinical development of this combination for tumors intrinsically resistant to PARP inhibitors and radiotherapy. 展开更多
关键词 NSCLC PARP BLM RADIOSENSITIZATION homologous recombination repair
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Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer 被引量:2
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作者 Yimeng Chen Xue Wang +8 位作者 Feng Du Jian Yue Yiran Si Xiaochen Zhao Lina Cui Bei Zhang Ting Bei Binghe Xu Peng Yuan 《Cancer Biology & Medicine》 SCIE CAS CSCD 2023年第2期155-168,共14页
Objective:The choice of chemotherapeutic regimen for triple-negative breast cancer(TNBC)remains controversial.Homologous recombination deficiency(HRD)has attracted increasing attention in informing chemotherapy treatm... Objective:The choice of chemotherapeutic regimen for triple-negative breast cancer(TNBC)remains controversial.Homologous recombination deficiency(HRD)has attracted increasing attention in informing chemotherapy treatment.This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy.Methods:Chinese patients with TNBC who received chemotherapy between May 1,2008 and March 31,2020 were retrospectively analyzed with a customized 3D-HRD panel.HRD positivity was defined by an HRD score≥30 or deleterious BRCA1/2 mutation.A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort(NCT01150513)and a metastatic cohort,and 189 patients with available clinical and tumor sequencing data were included.Results:In the entire cohort,49.2%(93/189)of patients were identified as HRD positive(40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of≥30).In the first-line metastatic setting,platinum therapy was associated with longer median progression-free survival(mPFS)than platinum-free therapy[9.1 vs.3.0 months;hazard ratio(HR),0.43;95%confidence interval 0.22–0.84;P=0.01].Among HRD-positive patients,the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy(13.6 vs.2.0 months;HR,0.11;P=0.001).Among patients administered a platinum-free regimen,HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients(P=0.02;treatment-biomarker P-interaction=0.001).Similar results were observed in the BRCA1/2-intact subset.In the adjuvant setting,HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy(P=0.05,P-interaction=0.02).Conclusions:HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings. 展开更多
关键词 homologous recombination deficiency triple-negative breast cancer PLATINUM SURVIVAL BRCA
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miR-506: a regulator of chemo-sensitivity through suppression of the RAD51-homologous recombination axis 被引量:4
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作者 Guoyan Liu Fengxia Xue Wei Zhang 《Chinese Journal of Cancer》 SCIE CAS CSCD 2015年第11期485-487,共3页
Ovarian carcinoma is the most lethal gynecologic malignancy. Resistance to platinum is considered the major problem afecting prognosis. Our recent study established that micro RNA-506(mi R-506) expression was closely ... Ovarian carcinoma is the most lethal gynecologic malignancy. Resistance to platinum is considered the major problem afecting prognosis. Our recent study established that micro RNA-506(mi R-506) expression was closely associated with progression-free survival and overall survival in two independent patient cohorts totaling 598 epithelial ovarian cancer cases. Further functional study demonstrated that mi R-506 could augment the response to cisplatin and olaparib through targeting RAD51 and suppressing homologous recombination in a panel of ovarian cancer cell lines. Systemic delivery of mi R-506 in an orthotopic ovarian cancer mouse model signiicantly augmented the cisplatin response, thus recapitulating the clinical observation. Therefore, mi R-506 plays a functionally important role in homologous recombination and has important therapeutic value for sensitizing cancer cells to chemotherapy, especially in chemo-resistant patients with attenuated expression of mi R-506. 展开更多
关键词 MicroRNA-506 homologous recombination DRUG sensitivity Synthetic lethality RAD51
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Maternal gene Ooep may participate in homologous recombination-mediated DNA double-strand break repair in mouse oocytes 被引量:1
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作者 Da-Jian He Lin Wang +5 位作者 Zhi-Bi Zhang Kun Guo Jing-Zheng Li Xie-Chao He Qing-Hua Cui Ping Zheng 《Zoological Research》 SCIE CAS CSCD 2018年第6期387-395,共9页
DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB r... DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase (RAD51) focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging. 展开更多
关键词 Ooep homologous recombination DNA double-strand break repair ATM RAD51
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Inhibition of KU70 and KU80 by CRISPR interference,not NgAgo interference,increases the efficiency of homologous recombination in pig fetal fibroblasts 被引量:2
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作者 LI Guo-ling QUAN Rong +10 位作者 WANG Hao-qiang RUAN Xiao-fang MO Jian-xin ZHONG Cui-li YANG Huaqiang LI Zi-cong GU Ting LIU De-wu WU Zhen-fang CAI Geng-yuan ZHANG Xian-wei 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2019年第2期438-448,共11页
Non-homologous end-joining(NHEJ) is a predominant pathway for the repair of DNA double-strand breaks(DSB). It inhibits the efficiency of homologous recombination(HR) by competing for DSB targets. To improve the effici... Non-homologous end-joining(NHEJ) is a predominant pathway for the repair of DNA double-strand breaks(DSB). It inhibits the efficiency of homologous recombination(HR) by competing for DSB targets. To improve the efficiency of HR, multiple CRISPR interference(CRISPRi) and Natronobacterium gregoryi Argonaute(NgAgo) interference(NgAgoi) systems have been designed for the knockdown of NHEJ key molecules, KU70, KU80, polynucleotide kinase/phosphatase(PNKP), DNA ligase IV(LIG4), and NHEJ1. Suppression of KU70 and KU80 by CRISPRi dramatically promoted(P<0.05) the efficiency of HR to 1.85-and 1.58-fold, respectively, whereas knockdown of PNKP, LIG4, and NHEJ1 repair factors did not significantly increase(P>0.05) HR efficiency. Interestingly, although the NgAgoi system significantly suppressed(P<0.05) KU70, KU80, PNKP, LIG4, and NHEJ1 expression, it did not improve(P>0.05) HR efficiency in primary fetal fibroblasts. Our result showed that both NgAgo and catalytically inactive Cas9(dCas9) could interfere with the expression of target genes, but the downstream factors appear to be more active following CRISPR-mediated interference than that of NgAgo. 展开更多
关键词 homologous recombination non-homologous end-joining CRISPRi NgAgoi KU70 KU80
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Targeting of human aFGF gene into silkworm,Bombyx mori L. through homologous recombination 被引量:10
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作者 吴小锋 曹翠平 《Journal of Zhejiang University Science》 EI CSCD 2004年第6期644-650,共7页
The long-arm and short-arm genes of fibroin light chain (L-chain) of silkworm, Bombyx Mori L., and the gene of human acidic fibroblast growth factor were cloned respectively and subsequently inserted into a transfer v... The long-arm and short-arm genes of fibroin light chain (L-chain) of silkworm, Bombyx Mori L., and the gene of human acidic fibroblast growth factor were cloned respectively and subsequently inserted into a transfer vector pVL 1392 used as a tool to target the L-chain region of the silkworm genome. Genomic DNA from their offsprings was extracted and the expected targeting was detected using polymerase chain reaction and DNA sequencing, as well as protein analysis. The results showed that positive events occurred and that the FGF gene was integrated into the L-chain locus through homologous recombination. 展开更多
关键词 Gene targeting Recombinant vector Bombyx mori L.
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Phylogeny and Homologous Recombination in Japanese Encephalitis Viruses
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作者 Li Xiao-xue Cong Ying-ying +4 位作者 Wang Xin Ren Yu-dong Ren Xiao-feng Lu Ai-guo Li Guang-xing 《Journal of Northeast Agricultural University(English Edition)》 CAS 2015年第1期40-49,共10页
Japanese encephalitis virus(JEV) is a significant causative agent of arthropod-borne encephalitis and what is less clear that the factors cause the virus wide spread. The objective was to confirm whether the homolog... Japanese encephalitis virus(JEV) is a significant causative agent of arthropod-borne encephalitis and what is less clear that the factors cause the virus wide spread. The objective was to confirm whether the homologous recombination imposed on JEV. The phylogenetic and homologous recombination analyses were performed based on 163 complete JEV genomes which were recently isolated. They were still separated into five genotypes(GI-GV) and the most of recently isolated JEVs were GI rather than GIII in Asian areas including China's Mainland. Two recombinant events were identified in JEV and the evidence of the recombination was observed between China and Japan isolates that partitioned into two distinct subclades, but still the same genotype(GIII). Our data further suggested that most of the nucleotides in JEV genome were under negative selection; however, changes within codon 2 316(amino acid NS4b-44) showed an evidence of the positive selection. 展开更多
关键词 Japanese encephalitis virus PHYLOGENY homologous recombination
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Phylogeny and Homologous Recombination Occurring in Classical Swine Fever Viruses
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作者 Jiang Qing-yun Gao Yu +4 位作者 Li Wei-qun Ding Fan Juergen Richt Ren Yu-dong Li Guang-xing 《Journal of Northeast Agricultural University(English Edition)》 CAS 2019年第3期57-65,共9页
Classical swine fever virus(CSFV) is the causative agent of classical swine fever, a highly contagious disease of pigs. But there is little information on the recombination in natural populations of CSFVs. Therefore, ... Classical swine fever virus(CSFV) is the causative agent of classical swine fever, a highly contagious disease of pigs. But there is little information on the recombination in natural populations of CSFVs. Therefore, a phylogenetic analysis of 62 fulllength genome CSFV strains, isolated from all over the world, was performed to detect potential recombination events, with the recombinant sequences being analyzed with the SimPlot and RDP programs. The results identified a mosaic virus, Chinese CSFV HCLV(2)(AF091507.1), which is the one naturally emerged recombinant CSFV with two recombination breakpoints at 2 484 and 2 900 bp of the genome alignment. Its two putative parental-like strains were CSFV Shimen(AF092448.2) and CSFV strain C/HVRI(AY805221.1). This work demonstrated that homologous recombination did occur in natural CSFV populations. It had significant implications for understanding the molecular epidemiology of CSFV, and revealed that recombination was an important factor for high genetic diversities of CSFV. 展开更多
关键词 CLASSICAL SWINE FEVER virus homologous recombination PHYLOGENY genetic diversity
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Histological Assessment of Bone Regeneration in the Maxilla with Homologous Bone Graft:A Feasible Option for Maxillary Bone Reconstruction
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作者 Sergio Henrique Gonçalves Motta Ana Paula Ramos Soares +1 位作者 Juliana Campos Hasse Fernandes Gustavo Vicentis Oliveira Fernandes 《Journal of Renewable Materials》 EI CAS 2024年第1期131-148,共18页
Bone biomaterials have been increasingly used to reconstruct maxillary atrophic ridges.Thus,the aim of this study was to evaluate bone reconstruction in the maxilla using a homologous cortico-cancellous FFB(lyophilize... Bone biomaterials have been increasingly used to reconstruct maxillary atrophic ridges.Thus,the aim of this study was to evaluate bone reconstruction in the maxilla using a homologous cortico-cancellous FFB(lyophilized)graft and verify its reliability.Eight individuals were included from 2014 to 2018.The first surgery was performed to install homologous bone blocks in the maxilla.The period of the second intervention varied between 5 months and 15 days to 11 months(≈7.93 months).The biopsies were taken from the central region of the matured graft during the surgery for implant placement.All patients presented clinical and radiographic conditions for the installation of dental implants.There was a 100%of survival rate.The histological assessment showed that the homologous block bone graft was an osteoconductive biomaterial,with connective tissue present,and newly formed bone juxtaposed on its surface.There were bone trabeculae with osteocytes and active osteoblasts with connective tissue in the mineralization process;the remodeling process can be found through the reverse lines.A limited focus of necrosis with fibrosis was detected,with small resorption and areas of inflammatory infiltrate,but without clinical significance.The homologous block bone graft can be considered a feasible option to substitute the autogenous bone graft(gold standard),with predictable clinical and favorable histological results.The patients had a shorter surgical period,low morbidity,and an unlimited amount of biomaterial available at an accessible cost. 展开更多
关键词 Regeneration bone graft HISTOLOGY homologous allogenous AUTOGENOUS
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Initial measurement of ultrafast charge exchange recombination spectroscopy on the EAST tokamak
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作者 蒋军 李颖颖 +5 位作者 陈冉 符佳 吕波 余羿 徐国盛 叶民友 《Plasma Science and Technology》 SCIE EI CAS CSCD 2024年第5期40-46,共7页
Ultrafast charge exchange recombination spectroscopy(UF-CXRS)has been developed on the EAST tokamak(Yingying Li et al 2019 Fusion Eng.Des.146522)to measure fast evolutions of ion temperature and toroidal velocity.Here... Ultrafast charge exchange recombination spectroscopy(UF-CXRS)has been developed on the EAST tokamak(Yingying Li et al 2019 Fusion Eng.Des.146522)to measure fast evolutions of ion temperature and toroidal velocity.Here,we report the preliminary diagnostic measurements after relative sensitivity calibration.The measurement results show a much higher temporal resolution compared with conventional CXRS,benefiting from the usage of a prismcoupled,high-dispersion volume-phase holographic transmission grating and a high quantum efficiency,high-gain detector array.Utilizing the UF-CXRS diagnostic,the fast evolutions of the ion temperature and rotation velocity during a set of high-frequency small-amplitude edgelocalized modes(ELMs)are obtained on the EAST tokamak,which are then compared with the case of large-amplitude ELMs. 展开更多
关键词 ultrafast charge exchange recombination spectroscopy EAST diagnostic measurements
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Mechanochemical strategy assisted morphology recombination of COFs for promoted kinetics and LiPS transformation in Li-S batteries
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作者 Yunchen Ge Yan Meng +3 位作者 Lin Liu Jianming Li Xuechun Huang Dan Xiao 《Green Energy & Environment》 SCIE EI CAS CSCD 2024年第12期1822-1834,共13页
A covalent organic frameworks(COFs)material with regular pores and stable structure can be used as the host of lithium-sulfur batteries to improve battery kinetics and polysulfides conversion.Herein,we designed and sy... A covalent organic frameworks(COFs)material with regular pores and stable structure can be used as the host of lithium-sulfur batteries to improve battery kinetics and polysulfides conversion.Herein,we designed and synthesized two kinds of rod-liked bulk COFs by adjusting different pore sizes(COF-BTD and COF-TFB),unfortunately,the active sites masking and sluggish kinetics have not met our expectations.Generally,the available layered COFs prepared from mechanochemical can expose abundant active sites and favorable kinetics than bulk COFs.Thus,simple mechanical ball milling is applied to activate the above COFs(M-COFs group).It is worth noting that layered R-COF-BTD is directly synthesized from rod-liked precursors by simple morphological reconstruction.A series of characterization methods are used to systematically explore the advantages of the group of M-COFs@S electrodes in the cycling process,including the effects of specific morphology on the kinetics and transformation of polysulfides.Our research provides a feasible plan for the development and selection of the host material of lithium-sulfur batteries. 展开更多
关键词 Covalent organic frameworks Ball milling recombination of morphology Li–S batteries
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Physico−mathematical model of the voltage−current characteristics of light-emitting diodes with quantum wells based on the Sah−Noyce−Shockley recombination mechanism
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作者 Fedor I.Manyakhin Dmitry O.Varlamov +3 位作者 Vladimir P.Krylov Lyudmila O.Morketsova Arkady A.Skvortsov Vladimir K.Nikolaev 《Journal of Semiconductors》 EI CAS CSCD 2024年第8期25-33,共9页
Herein,a physical and mathematical model of the voltage−current characteristics of a p−n heterostructure with quantum wells(QWs)is prepared using the Sah−Noyce−Shockley(SNS)recombination mechanism to show the SNS reco... Herein,a physical and mathematical model of the voltage−current characteristics of a p−n heterostructure with quantum wells(QWs)is prepared using the Sah−Noyce−Shockley(SNS)recombination mechanism to show the SNS recombination rate of the correction function of the distribution of QWs in the space charge region of diode configuration.A comparison of the model voltage−current characteristics(VCCs)with the experimental ones reveals their adequacy.The technological parameters of the structure of the VCC model are determined experimentally using a nondestructive capacitive approach for determining the impurity distribution profile in the active region of the diode structure with a profile depth resolution of up to 10Å.The correction function in the expression of the recombination rate shows the possibility of determining the derivative of the VCCs of structures with QWs with a nonideality factor of up to 4. 展开更多
关键词 light-emitting diodes with quantum wells voltage−current relation nonideality factor recombination mechanism Sah−Noyce−Shockley model
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Features of Recombination Radiation of GaAs Type Semiconductors with the Participation of Fine Acceptor Levels in a Magnetic Field
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作者 Nosirjon Khaydarovich Yuldashev Iftixorjon Isaqovich Yulchiev +1 位作者 Bozorboy Joboraliyevich Akhmadaliev Khusanboy Manopovich Sulaymonov 《Journal of Applied Mathematics and Physics》 2024年第7期2407-2420,共14页
Using the method of Picus and Beer invariants, general expressions are obtained for the total intensity I and the degree of circular polarization Рcirc.of the luminescence of GaAs-type semiconductors with the partici... Using the method of Picus and Beer invariants, general expressions are obtained for the total intensity I and the degree of circular polarization Рcirc.of the luminescence of GaAs-type semiconductors with the participation of shallow acceptor levels in a longitudinal magnetic field H. Special cases are analyzed depending on the value and direction of the magnetic field strength, as well as on the constants of the g-factor of the acceptor g1,g2and the conduction band electron ge. In the case of a strong magnetic field H// [100], [111], [110], a numerical calculation of the angular dependence of the quantities I and Рcirc.was performed for some critical values of g2/g1, at which Рcirc.exhibits a sharp anisotropy in the range from −100% to +100%, and the intensity of the crystal radiation along the magnetic field tends to a minimum value. 展开更多
关键词 Semiconductor recombination Radiation Shallow Acceptor Center Magnetic Field Zeeman Splitting G-FACTORS Anisotropy Circular Polarization Intensity
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