KCTD10 is a sensor for co-directional transcription-replication conflicts.

ABSTRACT: During DNA replication, the replisome must remove barriers and roadblocks including the transcription machinery^1,2. Transcription-replication conflicts (TRCs) occur when there are collisions between the replisome and transcription machinery, and are increasingly recognized as an important source of mammalian genome instability³. How cells facilitate replisome bypass at sites of TRCs is incompletely understood. Here we show that the CUL3-KCTD10 E3 ligase senses TRCs and promotes remodelling of the RNA polymerase complex to allow replisome bypass. We found that the substrate adaptor KCTD10 interacts with the replisome and the transcription machinery and regulates both in unstressed conditions. These bivalent interactions allow KCTD10 to detect co-directional TRCs and fa

SUBMITTER: Kloeber JA 

PROVIDER: S-EPMC12675284 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature