The SMC5/SMC6 complex is critical for resolving R-loop-induced transcription-replication conflicts.

ABSTRACT: R-loops play essential physiological roles but also pose a significant threat to genome stability, particularly during replication, by exacerbating transcription-replication conflicts (TRCs). In this study, we have uncovered a critical role of the SMC5/6 complex in resolving TRCs to preserve fork integrity. We identified the SMC5/6 complex as a synthetic lethal partner of senataxin (SETX), an RNA/DNA helicase critical for removing R-loops that arise during replication. We demonstrated that in SETX-deficient cells, the SMC5/6 complex is recruited to TRCs in response to the buildup of DNA supercoiling and facilitates the recruitment of the BLM/TOP3A/RMI1/RMI2 complex (BTRR). Once recruited, BTRR acts to resolve the TRCs in a manner dependent on the catalytic activity of TOP3A. BTRR is also r

SUBMITTER: Wu T 

PROVIDER: S-EPMC12802942 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature