Rad51/RadA paralogs found in eukaryotes and euryarchaea play important roles during recombination and repair,and mutations in one of the human Rad51 paralogs,Rad51C,are associated with breast and ovarian cancers.The h...Rad51/RadA paralogs found in eukaryotes and euryarchaea play important roles during recombination and repair,and mutations in one of the human Rad51 paralogs,Rad51C,are associated with breast and ovarian cancers.The hyperthermophilic crenarchaeon Sulfolobus tokodaii encodes four putative RadA paralogs and studies on these proteins may assist in understanding the functions of human Rad51 paralogs.Here,we report the biochemical characterization of stRadC2,a S.tokodaii RadA paralog.Pull-down assays revealed that the protein was able to interact with the recombinase,RadA,and the Holliday junction endonuclease,Hjc.stRadC2 inhibited the strand exchange activity of RadA and facilitated Hjc-mediated Holliday junction DNA cleavage in vitro.RT-PCR analysis revealed that stRadC2 transcription was immediately reduced after UV irradiation,but was restored to normal levels at the late stages of DNA repair.Our results suggest that stRadC2 may act as an anti-recombination factor in DNA recombinational repair in S.tokodaii.展开更多
Meiosis comprises two rounds of nuclear division following a single phase of DNA replication, leading to the production of haploid gametes and is essential for sexual reproduction in eukaryotes. Unlike mitosis, meiosi...Meiosis comprises two rounds of nuclear division following a single phase of DNA replication, leading to the production of haploid gametes and is essential for sexual reproduction in eukaryotes. Unlike mitosis, meiosis involves homologous chromosome pairing, synapsis, and recombination during prophase I. Meiotic recombination not only ensures the accurate segregation of homologs, but also redistributes alleles among offspring. DNA synthesis is a critical process during meiotic recombination, but our understanding of the proteins that execute and regulate it is limited. This review summarizes the recent advances in defining the role of DNA synthesis in meiotic recombina- tion through analyses of DNA synthesis genes, with specific emphasis on DNA polymerases (e.g., Pole and PolS), replication processivity factor RFC1 and translesion polymerases (e.g., Pol~). We also present a new double strand break repair model for meiotic recombination, which includes lagging strand DNA synthesis and leading strand elongation. Finally, we propose that DNA synthesis is one of critical factors for discriminating meiotic recombination pathways and that this differentiation may be conserved among eukaryotes.展开更多
基金supported by the National Natural Science Foundation of China (Grant Nos. 3093002 and 30870046 to Shen YuLong,and 30700011 to Sheng DuoHong)the Promotive Research Fund for Excellent Young and Middle-aged Scientists of Shandong Province (Grant No. BS2010SW014 to Sheng DuoHong)
文摘Rad51/RadA paralogs found in eukaryotes and euryarchaea play important roles during recombination and repair,and mutations in one of the human Rad51 paralogs,Rad51C,are associated with breast and ovarian cancers.The hyperthermophilic crenarchaeon Sulfolobus tokodaii encodes four putative RadA paralogs and studies on these proteins may assist in understanding the functions of human Rad51 paralogs.Here,we report the biochemical characterization of stRadC2,a S.tokodaii RadA paralog.Pull-down assays revealed that the protein was able to interact with the recombinase,RadA,and the Holliday junction endonuclease,Hjc.stRadC2 inhibited the strand exchange activity of RadA and facilitated Hjc-mediated Holliday junction DNA cleavage in vitro.RT-PCR analysis revealed that stRadC2 transcription was immediately reduced after UV irradiation,but was restored to normal levels at the late stages of DNA repair.Our results suggest that stRadC2 may act as an anti-recombination factor in DNA recombinational repair in S.tokodaii.
基金Acknowledgments We apologize to colleagues whose work could not be cited owing to space constraints. J.H., H.M. and Y.W. are supported by the Ministry of Science and Technology of China (2011CB944603), the National Natural Science Foundation of China (31370347), and by funds from Fudan University and Rijk Zwaan. G.P.C. is supported by the US National Science Foundation (MCB- 1121563) and Rijk Zwaan.
文摘Meiosis comprises two rounds of nuclear division following a single phase of DNA replication, leading to the production of haploid gametes and is essential for sexual reproduction in eukaryotes. Unlike mitosis, meiosis involves homologous chromosome pairing, synapsis, and recombination during prophase I. Meiotic recombination not only ensures the accurate segregation of homologs, but also redistributes alleles among offspring. DNA synthesis is a critical process during meiotic recombination, but our understanding of the proteins that execute and regulate it is limited. This review summarizes the recent advances in defining the role of DNA synthesis in meiotic recombina- tion through analyses of DNA synthesis genes, with specific emphasis on DNA polymerases (e.g., Pole and PolS), replication processivity factor RFC1 and translesion polymerases (e.g., Pol~). We also present a new double strand break repair model for meiotic recombination, which includes lagging strand DNA synthesis and leading strand elongation. Finally, we propose that DNA synthesis is one of critical factors for discriminating meiotic recombination pathways and that this differentiation may be conserved among eukaryotes.