Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis

Rad51 plays a central role in homologous recombination pathways. Now work with Xenopus laevis egg extracts shows that Rad51 prevents formation of DNA gaps at or behind replication forks, which are dependent on Mre11 nuclease activity. The role of Rad51 in an unperturbed cell cycle has been difficult...

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Vydáno v:	Nature structural & molecular biology Ročník 17; číslo 11; s. 1305 - 1311
Hlavní autoři:	Hashimoto, Yoshitami, Ray Chaudhuri, Arnab, Lopes, Massimo, Costanzo, Vincenzo
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.11.2010 Nature Publishing Group
Témata:	631/337/1427 631/337/151 Animals Biochemistry Biological Microscopy Biomedical and Life Sciences Biosynthesis Cell cycle Cellular proteins Chromatin - metabolism Deoxyribonucleic acid DNA DNA Damage DNA repair DNA replication DNA Replication - physiology DNA synthesis DNA, Single-Stranded - metabolism DNA, Single-Stranded - ultrastructure DNA-Binding Proteins - antagonists & inhibitors DNA-Binding Proteins - physiology Life Sciences Membrane Biology Molecular biology MRE11 Homologue Protein Proliferating Cell Nuclear Antigen - physiology Properties Protein Structure Proteolysis Rad51 Recombinase - metabolism Rad51 Recombinase - physiology Xenopus laevis Xenopus Proteins - antagonists & inhibitors Xenopus Proteins - metabolism Xenopus Proteins - physiology United Kingdom Switzerland
ISSN:	1545-9993, 1545-9985, 1545-9985
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Shrnutí:	Rad51 plays a central role in homologous recombination pathways. Now work with Xenopus laevis egg extracts shows that Rad51 prevents formation of DNA gaps at or behind replication forks, which are dependent on Mre11 nuclease activity. The role of Rad51 in an unperturbed cell cycle has been difficult to distinguish from its DNA repair function. Here, using EM to visualize replication intermediates assembled in Xenopus laevis egg extract, we show that Rad51 is required to prevent the accumulation of single-stranded DNA (ssDNA) gaps at replication forks and behind them. ssDNA gaps at forks arise from extended uncoupling of leading- and lagging-strand DNA synthesis. In contrast, ssDNA gaps behind forks, which are prevalent on damaged templates, result from Mre11-dependent degradation of newly synthesized DNA strands and are suppressed by inhibition of Mre11 nuclease activity. These findings reveal direct roles for Rad51 at replication forks, demonstrating that Rad51 protects newly synthesized DNA from Mre11-dependent degradation and promotes continuous DNA synthesis.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 AUTHOR CONTRIBUTIONS Y.H. and A.R.C performed experiments; M.L and V.C conceived experiments and wrote the manuscript.
ISSN:	1545-9993 1545-9985 1545-9985
DOI:	10.1038/nsmb.1927