RRM1 promotes homologous recombination and radio/chemo-sensitivity via enhancing USP11 and E2F1-mediated RAD51AP1 transcription.

ABSTRACT: Ribonucleotide reductase M1 (RRM1), the catalytic subunit of ribonucleotide reductase, plays a pivotal role in converting ribonucleotides (NTP) into deoxyribonucleotides (dNTP), essential for DNA replication and repair. Elevated RRM1 expression is associated with various human cancers, correlating with poorer prognosis and reduced overall survival rates. Our previous study found that RRM1 will enter the nucleus to promote DNA damage repair. However, the underlying mechanism remains elusive. Here, we unveil a novel role of RRM1 in promoting homologous recombination (HR) by upregulating the expression of RAD51AP1, a critical HR factor, in an E2F1-dependent manner. We demonstrate that RRM1 interacts with USP11 in the cytoplasm, and the recruitment of RRM1 to LaminB1 induced by ionizing radiat

SUBMITTER: Yang S 

PROVIDER: S-EPMC11655868 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature