DCAF14 Promotes Stalled Fork Stability to Maintain Genome Integrity

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2021 Jan 27

PMID 33503431

Citations 11

Authors

Arik Townsend

Gabriella Lora

Justin Engel

Neysha Tirado-Class

Huzefa Dungrawala

Affiliations

Soon will be listed here.

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 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.

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