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RAD52 Prevents Excessive Replication Fork Reversal and Protects from Nascent Strand Degradation
- Source :
- Nature Communications, Vol 10, Iss 1, Pp 1-19 (2019), Nature Communications
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Stabilisation of stalled replication forks prevents excessive fork reversal and their pathological degradation, which can undermine genome integrity. Here we investigate a physiological role of RAD52 at stalled replication forks by using human cell models depleted of RAD52, a specific small-molecule inhibitor of the RAD52-ssDNA interaction, in vitro and single-molecule analyses. We demonstrate that RAD52 prevents excessive degradation of reversed replication forks by MRE11. Mechanistically, RAD52 binds to the stalled replication fork, promotes its occlusion and counteracts loading of SMARCAL1 in vitro and in vivo. Loss of the RAD52 function results in a slightly-defective replication restart, persistence of under-replicated regions and chromosome instability. Moreover, the RAD52-inhibited cells rely on RAD51 for completion of replication and viability upon replication arrest. Collectively, our data suggest an unexpected gatekeeper mechanism by which RAD52 limits excessive remodelling of stalled replication forks, thus indirectly assisting RAD51 and BRCA2 in protecting forks from unscheduled degradation and preventing genome instability.<br />Stabilisation of stalled replication forks prevents excessive fork reversal and genome instability. Here authors reveal a RAD52-dependent replication fork protection mechanism.
- Subjects :
- DNA Replication
0301 basic medicine
Replication fork reversal
Genome instability
Genome integrity
DNA damage
Science
genetic processes
RAD52
RAD51
DNA, Single-Stranded
General Physics and Astronomy
02 engineering and technology
Models, Biological
Article
Genomic Instability
General Biochemistry, Genetics and Molecular Biology
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Chromosome instability
Humans
lcsh:Science
MRE11 Homologue Protein
Multidisciplinary
Chemistry
fungi
DNA Helicases
DNA replication
General Chemistry
021001 nanoscience & nanotechnology
Replication (computing)
Rad52 DNA Repair and Recombination Protein
Cell biology
enzymes and coenzymes (carbohydrates)
030104 developmental biology
lcsh:Q
Rad51 Recombinase
0210 nano-technology
DNA
DNA Damage
Degradation (telecommunications)
Subjects
Details
- ISSN :
- 15565068
- Database :
- OpenAIRE
- Journal :
- SSRN Electronic Journal
- Accession number :
- edsair.doi.dedup.....4f93c81cc3df332f252b13bac7fbe41c