HUWE 1 comes to the rescue at stalled replication forks

Abstract

HUWE 1 is a multi‐faceted E3 ubiquitin ligase of the HECT family with many confirmed substrates, but mechanistic understanding of its functional roles in signaling pathways remains limited. In this issue of EMBO Reports , Choe et al demonstrate a novel function for HUWE 1 in promoting DNA damage tolerance mechanisms to bypass DNA lesions during replication stress, thereby preserving genome stability. The authors connect this role for HUWE 1 with its function in maintaining H2 AX monoubiquitination levels for efficient signaling at stalled replication forks . Thus, this work highlights HUWE 1 as a novel player in the replication stress response and prompts further investigation of its regulation during replication and other cellular processes.