The Ski2 helicase ASCC3 unwinds DNA upon fork stalling to control replication stress responses.

ABSTRACT: The activating signal co-integrator 1 complex subunit 3 (ASCC3), the largest subunit of ASCC, is one of two Ski2-like helicases with duplicated helicase cassettes encoded by the human genome. ASCC3 has been implicated in transcriptional regulation, alkylation damage repair, and ribosome quality control. In addition, published proteomics studies suggest that ASCC3 is associated with stalled forks. However, little is known about its role in replication stress. Here we report that ASCC3 is recruited to stalled forks by its binding partner ASCC2, whose recruitment to stalled forks is dependent upon both its ubiquitin binding activity and polyubiquitylation of PCNA at K164 that is catalyzed by SHPRH, HLTF, and RFWD3. In response to replication stress. ASCC3 unwinds DNA, generating both parental

SUBMITTER: Cui S 

PROVIDER: S-EPMC12330601 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature