Journal article
Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation
Nature communications, Vol.10(1), pp.1412-1412
03/29/2019
DOI: 10.1038/s41467-019-09196-9
PMCID: PMC6441034
PMID: 30926821
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.
Details
- Title: Subtitle
- Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation
- Creators
- Eva Malacaria - Istituto Superiore di SanitàGiusj Monia Pugliese - Istituto Superiore di SanitàMasayoshi Honda - University of IowaVeronica Marabitti - Istituto Superiore di SanitàFrancesca Antonella Aiello - Istituto Superiore di SanitàMaria Spies - University of IowaAnnapaola Franchitto - Istituto Superiore di SanitàPietro Pichierri - Istituto Superiore di Sanità
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.10(1), pp.1412-1412
- DOI
- 10.1038/s41467-019-09196-9
- PMID
- 30926821
- PMCID
- PMC6441034
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- Springer Nature
- Number of pages
- 19
- Grant note
- P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NIH R01GM108617; NIH P30 CA086862 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM108617 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) IG17383; IG21428; IG15410 / Associazione Italiana per la Ricerca sul Cancro (AIRC); Fondazione AIRC per la ricerca sul cancro
- Language
- English
- Date published
- 03/29/2019
- Academic Unit
- Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984288720902771
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