Chromatin-Associated SIN3B Protects Cancer Cells from Genotoxic Stress-Induced Apoptosis and Dictates DNA Damage Repair Pathway Choice.

ABSTRACT: Transcription and DNA damage repair act in a coordinated manner. The scaffolding protein SIN3B serves as a transcriptional co-repressor of hundreds of cell cycle-related genes. However, the contribution of SIN3B during the DNA damage response remains unknown. Here, we show that SIN3B inactivation delays the resolution of DNA double-strand breaks and sensitizes cancer cells to DNA-damaging agents, including the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, SIN3B is rapidly recruited to DNA damage sites where it directs the accumulation of Mediator of DNA Damage Checkpoint 1 (MDC1). In addition, we show that SIN3B inactivation favors the engagement of the alternative nonhomologous end joining (NHEJ) repair pathway over the canonical NHEJ. Altogether, our findings impute

SUBMITTER: Morales-Valencia J 

PROVIDER: S-EPMC10527583 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature