BMI1 represses G-quadruplex DNA formation to maintain genomic stability during replication.

ABSTRACT: Single-stranded DNA secondary structures such as G-quadruplexes (G4s) can potentially disrupt transcription, replication, and repair. Using bioinformatic analysis, here, we show that BMI1 is enriched at putative G4s flanked by heterochromatin domains and that BMI1 knockdown in human dermal fibroblasts (HDFs) resulted in heterochromatin relaxation and G4 induction, followed by replication stress and genomic instability. In these cells, G4s co-localized with large 53BP1 and PCNA foci resembling replication catastrophes. Inhibiting transcription partly attenuated DNA damage, suggesting rescue of transcription-replication collisions at difficult-to-replicate sequences. In BMI1 knockdown or pyridostatin-exposed HDFs, the Werner helicase accumulated and co-localized with G4s, and acute WRN knock

SUBMITTER: Hanna R 

PROVIDER: S-EPMC12919260 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature