DCAF14 promotes stalled fork stability to maintain genome integrity.

Arik Townsend, Gabriella Lora, Justin Engel, Neysha Tirado-Class, Huzefa Dungrawala

Cell reports 2021 Jan 26

filter terms:

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, CRL4DCAF14 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. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Arik Townsend, Gabriella Lora, Justin Engel, Neysha Tirado-Class, Huzefa Dungrawala. DCAF14 promotes stalled fork stability to maintain genome integrity. Cell reports. 2021 Jan 26;34(4):108669