Úloha RECQ5 helikázy při udržování stability genomu

Urban, Václav

DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. Collisions between replication and transcription machineries represent a significant source of genomic instability. RECQ5 DNA helicase binds to RNA-polymerase (RNAP) II during transcription elongation and suppresses transcription-associated genomic instability. Here we show that RECQ5 also associates with RNAPI and enforces the stability of ribosomal DNA arrays in cells exposed to replication stress. We demonstrate that RECQ5 associates with transcription complexes in DNA replication foci and counteracts replication fork stalling in RNAPI- and RNAPII-transcribed genes, suggesting that RECQ5 exerts its genome stabilizing effect by acting at sites of concomitant replication and transcription. Moreover, RECQ5- deficient cells accumulate RAD51 foci that are formed in a BRCA1-dependent manner at sites of interference between replication and transcription and likely represent unresolved replication intermediates. Importantly, BRCA1-dependent formation...

guest :: login Digital Repository
		Search		Submit		Help		About