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...

Full description

Saved in:
Bibliographic Details
Published in:Nature structural & molecular biology Vol. 17; no. 11; pp. 1305 - 1311
Main Authors: Hashimoto, Yoshitami, Ray Chaudhuri, Arnab, Lopes, Massimo, Costanzo, Vincenzo
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.11.2010
Nature Publishing Group
Subjects:
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography: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