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DCAF14 promotes stalled fork stability to maintain genome integrity.

ABSTRACT: Replication stress response ensures impediments to DNA replication do not compromise replication fork stability and genome integrity. In a process termed replication fork protection, newly synthesized DNA at stalled replication forks is stabilized and protected from nuclease-mediated degradation. We report the identification of DDB1- and CUL4-associated factor 14 (DCAF14), a substrate receptor for Cullin4-RING E3 ligase (CRL4) complex, integral in stabilizing stalled replication forks. DCAF14 localizes rapidly to stalled forks and promotes genome integrity by preventing fork collapse into double-strand breaks (DSBs). Importantly, CRL4^DCAF14 mediates stalled fork protection in a RAD51-dependent manner to protect nascent DNA from MRE11 and DNA2 nucleases. Thus, our study shows replication stress response functions of DCAF14 in genome maintenance.

SUBMITTER: Townsend A

PROVIDER: S-EPMC7941590 | biostudies-literature |

REPOSITORIES: biostudies-literature

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