BLM prevents instability of structure-forming DNA sequences at common fragile sites.

摘要: Genome instability often arises at common fragile sites (CFSs) leading to cancer-associated chromosomal rearrangements. However, the underlying mechanisms of how CFS protection is achieved not well understood. We demonstrate that BLM plays an important role in maintenance genome stability structure-forming AT-rich sequences derived from CFSs (CFS-AT). deficiency leads increased DSB formation and hyper mitotic recombination CFS-AT induces plasmids containing CFS-AT. further showed required for suppression breakage upon oncogene expression. Both helicase activity ATR-mediated phosphorylation are preventing genetic sequences. Furthermore, protecting epistatic FANCM, a translocase involved preserving stability. Loss drastic decrease cell viability FANCM deficient cells. propose utilize different remove DNA secondary structures forming on replication forks, thereby maintaining