Unknown

Dataset Information

0

Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation.


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.

SUBMITTER: Malacaria E 

PROVIDER: S-EPMC6441034 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation.

Malacaria Eva E   Pugliese Giusj Monia GM   Honda Masayoshi M   Marabitti Veronica V   Aiello Francesca Antonella FA   Spies Maria M   Franchitto Annapaola A   Pichierri Pietro P  

Nature communications 20190329 1


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, RAD5  ...[more]

Similar Datasets

| S-EPMC9868089 | biostudies-literature
| S-EPMC10402051 | biostudies-literature
| S-EPMC5643541 | biostudies-literature
| S-EPMC7809791 | biostudies-literature
| S-EPMC9882250 | biostudies-literature
| S-EPMC10325910 | biostudies-literature
| S-SCDT-EMBOJ-2019-103654 | biostudies-other
| S-EPMC8286330 | biostudies-literature
| S-EPMC3320595 | biostudies-literature
| S-EPMC7397735 | biostudies-literature