Non-enzymatic roles of human RAD51 at stalled replication forks

The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not D-loop activity, to reveal mechanistic aspects of RAD51’s roles in the resp...

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Bibliographic Details
Published in:Nature communications 2019-09, Vol.10 (1), p.4410-11, Article 4410
Main Authors: Mason, Jennifer M., Chan, Yuen-Ling, Weichselbaum, Ralph W., Bishop, Douglas K.
Format: Article
Language:English
Subjects:
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Binding sites
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - genetics
DNA - metabolism
DNA Replication
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Enzymatic activity
Exchanging
Genomes
Humanities and Social Sciences
Humans
Models, Genetic
MRE11 protein
multidisciplinary
Mutation
Nucleic Acid Conformation
Proteins
Rad51 Recombinase - genetics
Rad51 Recombinase - metabolism
Recombination
Regression models
Replication
Replication forks
Roles
Science
Science (multidisciplinary)
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Summary:The central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not D-loop activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. Here, we find that cells lacking RAD51’s enzymatic activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly, we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication fork regression, supporting a model in which fork regression depends on a non-enzymatic function of RAD51. We also show RAD51 promotes replication restart by both strand exchange-dependent and strand exchange-independent mechanisms. RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, authors reveal mechanistic aspects of non-enzymatic roles of RAD51 for fork reversal and cooperation with FBH1.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-12297-0