In higher eukaryotes,DNA replication ensures precise transmission of genetic information from parental DNA to progeny,and the correct selection of replication origins is a critical step in this process.A very recent s...In higher eukaryotes,DNA replication ensures precise transmission of genetic information from parental DNA to progeny,and the correct selection of replication origins is a critical step in this process.A very recent study has shown that nucleosomes containing histone variant H2A.Z recruit SUV420H1,a histone H4 lysine 20 specific methyltransferase.Moreover,SUV420H1 promotes the H4K20 dimethylation,which can recruit the origin recognition complex to fulfill the selection and licensing of the replication origins.展开更多
DNA is generally assumed as a right-handed double helix and Z-DNA is a special kind of left-handed DNA infrequently found in nature. However, the finding of a zero linking number topoisomer supports a hypothesis that ...DNA is generally assumed as a right-handed double helix and Z-DNA is a special kind of left-handed DNA infrequently found in nature. However, the finding of a zero linking number topoisomer supports a hypothesis that the two strands of DNA are winding ambidextrously, rather than plectonemically. It logically leads to a notion that the left-handed DNA is as common as right-handed DNA and the amount of left-handed DNA in a positively supercoiled plasmid prevails that of the right-handed DNA. In this report, the helical repeat of left-handed DNA, 12 bp per turn, was determined by a new method. How the positively supercoiled DNA was generated in hyperthermophiles and why their DNA can withstand the extreme high temperature are answered from an alternative theory.展开更多
This study was directed on the B- into Z-DNA isomerization with alternating CG sequences monitored with artificial DNA model-systems based on methylation of the phosphate backbone. The chemical concept for this transi...This study was directed on the B- into Z-DNA isomerization with alternating CG sequences monitored with artificial DNA model-systems based on methylation of the phosphate backbone. The chemical concept for this transition wherein shielding of the oxygen anions of the backbone phosphates plays an essential role, resulted in the preparation of the phosphatemethylated d(CpG). Even on this primitive level of only two base pair long, the B-Z conformational aspects of this self-complementary duplex could be described in solution with nuclear magnetic resonance (NMR) and circular dichroism (CD) measurements. The exclusivity of this choice became clear after synthesizing phosphatemethylated DNA with longer alternating CG fragments. It could be shown that conflicting conformational effects of the CG and GC fragments resulted in an overall B structure of the phosphatemethylated tetramer d(CPGPCPG). From our model considerations, it is clear that the internal stress introduced by the alternating CG sequences will be promoted by a complete shielding of the phosphate backbone. Elimination of this effect may be realized by a site-specific phosphate shielding. The role of the anti-syn isomerization of G in the CG fragments is clarified by methylation of the phosphate group. This anti-syn transition is absent in corresponding methylphosphonates, suggesting an exclusive role for base-backbone coordination via hydrogen bonding. In addition, we propose that the B- into Z-DNA interconversion may offer a mechanistic view for differences in dynamics between cytosine and its epigenetic derivative 5-methylcytosine. This mechanism has been extended to the demethylation of 5-methylcytosine and the exchange of information between the new epigenetic base, 5-hydroxymethylcytosine and the DNA backbone via an intramolecular phosphorylation. The role of 5-hydroxymethylcytosine in Alzheimer disease has been briefly discussed. In our opinion, this study can be considered as a new dynamic concept for epigenetics based on the dynamics of the B-Z transition in natural and phosphatemethylated DNA.展开更多
Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed th...Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed the multi-Z method which uses 21 z-scores for each autosomal chromosome to detect aneuploidy of the chromosome, while the conventional NIPT method uses only one z-score. To do this, mapped read numbers of a certain chromosome were normalized by those of the other 21 chromosomes. Average and standard deviation (SD), which are used for calculating z-score of each sample, were obtained with normalized values between all autosomal chromosomes of control samples. In this way, multiple z-scores can be calculated for 21 autosomal chromosomes except oneself. Results: Multi-Z method showed 100% sensitivity and specificity for 187 samples sequenced to 3 M reads while the conventional NIPT method showed 95.1% specificity. Similarly, for 216 samples sequenced to 1 M reads, Multi-Z method showed 100% sensitivity and 95.6% specificity and the conventional NIPT method showed a result of 75.1% specificity. Conclusion: Multi-Z method showed higher accuracy and robust results than the conventional method even at low coverage reads.展开更多
We conducted genome sequence analysis to examine the presence/absence of two types of Z-DNA binding domains in various organisms. We examined 68 organisms from archaea, 914 organisms from bacteria, and 199 organisms f...We conducted genome sequence analysis to examine the presence/absence of two types of Z-DNA binding domains in various organisms. We examined 68 organisms from archaea, 914 organisms from bacteria, and 199 organisms from eukaryotes. RecA protein from Escherichia coli has a Z-DNA binding domain and this protein promotes homologous recombination. All the organisms examined had this domain. This result indicated that this domain is essential for all the organisms. RNA editing enzyme, adenosine deaminase from human has another type of Z-DNA binding domain. This domain was observed in some organisms of archaea, bacteria, and eukaryotes. The presence/absence of Z-DNA binding domain in adenosine deaminase indicated that gain and loss of this domain had occurred in the process of evolution. The implication of presence and absence of this domain is discussed in this study.展开更多
文摘In higher eukaryotes,DNA replication ensures precise transmission of genetic information from parental DNA to progeny,and the correct selection of replication origins is a critical step in this process.A very recent study has shown that nucleosomes containing histone variant H2A.Z recruit SUV420H1,a histone H4 lysine 20 specific methyltransferase.Moreover,SUV420H1 promotes the H4K20 dimethylation,which can recruit the origin recognition complex to fulfill the selection and licensing of the replication origins.
文摘DNA is generally assumed as a right-handed double helix and Z-DNA is a special kind of left-handed DNA infrequently found in nature. However, the finding of a zero linking number topoisomer supports a hypothesis that the two strands of DNA are winding ambidextrously, rather than plectonemically. It logically leads to a notion that the left-handed DNA is as common as right-handed DNA and the amount of left-handed DNA in a positively supercoiled plasmid prevails that of the right-handed DNA. In this report, the helical repeat of left-handed DNA, 12 bp per turn, was determined by a new method. How the positively supercoiled DNA was generated in hyperthermophiles and why their DNA can withstand the extreme high temperature are answered from an alternative theory.
文摘This study was directed on the B- into Z-DNA isomerization with alternating CG sequences monitored with artificial DNA model-systems based on methylation of the phosphate backbone. The chemical concept for this transition wherein shielding of the oxygen anions of the backbone phosphates plays an essential role, resulted in the preparation of the phosphatemethylated d(CpG). Even on this primitive level of only two base pair long, the B-Z conformational aspects of this self-complementary duplex could be described in solution with nuclear magnetic resonance (NMR) and circular dichroism (CD) measurements. The exclusivity of this choice became clear after synthesizing phosphatemethylated DNA with longer alternating CG fragments. It could be shown that conflicting conformational effects of the CG and GC fragments resulted in an overall B structure of the phosphatemethylated tetramer d(CPGPCPG). From our model considerations, it is clear that the internal stress introduced by the alternating CG sequences will be promoted by a complete shielding of the phosphate backbone. Elimination of this effect may be realized by a site-specific phosphate shielding. The role of the anti-syn isomerization of G in the CG fragments is clarified by methylation of the phosphate group. This anti-syn transition is absent in corresponding methylphosphonates, suggesting an exclusive role for base-backbone coordination via hydrogen bonding. In addition, we propose that the B- into Z-DNA interconversion may offer a mechanistic view for differences in dynamics between cytosine and its epigenetic derivative 5-methylcytosine. This mechanism has been extended to the demethylation of 5-methylcytosine and the exchange of information between the new epigenetic base, 5-hydroxymethylcytosine and the DNA backbone via an intramolecular phosphorylation. The role of 5-hydroxymethylcytosine in Alzheimer disease has been briefly discussed. In our opinion, this study can be considered as a new dynamic concept for epigenetics based on the dynamics of the B-Z transition in natural and phosphatemethylated DNA.
文摘Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed the multi-Z method which uses 21 z-scores for each autosomal chromosome to detect aneuploidy of the chromosome, while the conventional NIPT method uses only one z-score. To do this, mapped read numbers of a certain chromosome were normalized by those of the other 21 chromosomes. Average and standard deviation (SD), which are used for calculating z-score of each sample, were obtained with normalized values between all autosomal chromosomes of control samples. In this way, multiple z-scores can be calculated for 21 autosomal chromosomes except oneself. Results: Multi-Z method showed 100% sensitivity and specificity for 187 samples sequenced to 3 M reads while the conventional NIPT method showed 95.1% specificity. Similarly, for 216 samples sequenced to 1 M reads, Multi-Z method showed 100% sensitivity and 95.6% specificity and the conventional NIPT method showed a result of 75.1% specificity. Conclusion: Multi-Z method showed higher accuracy and robust results than the conventional method even at low coverage reads.
文摘We conducted genome sequence analysis to examine the presence/absence of two types of Z-DNA binding domains in various organisms. We examined 68 organisms from archaea, 914 organisms from bacteria, and 199 organisms from eukaryotes. RecA protein from Escherichia coli has a Z-DNA binding domain and this protein promotes homologous recombination. All the organisms examined had this domain. This result indicated that this domain is essential for all the organisms. RNA editing enzyme, adenosine deaminase from human has another type of Z-DNA binding domain. This domain was observed in some organisms of archaea, bacteria, and eukaryotes. The presence/absence of Z-DNA binding domain in adenosine deaminase indicated that gain and loss of this domain had occurred in the process of evolution. The implication of presence and absence of this domain is discussed in this study.
