GATA factor TRPS1, a new DNA repair protein, cooperates with reversible PARylation to promote chemoresistance in patients with breast cancer.

ABSTRACT: Resistance to DNA-damaging agents is a major unsolved challenge for breast cancer patients undergoing chemotherapy. Here, we show that elevated expression of transcriptional repressor GATA binding 1 (TRPS1) is associated with lower drug sensitivity, reduced response rate, and poor prognosis in chemotherapy-treated breast cancer patients. Mechanistically, elevated TRPS1 expression promotes hyperactivity of DNA damage repair (DDR) in breast cancer cells. We provide evidence that TRPS1 dynamically localizes to DNA breaks in a Ku70-and Ku80-dependent manner and that TRPS1 is a new member of the DDR protein family. We also discover that the dynamics of TRPS1 assembly at DNA breaks is regulated by its reversible PARylation in the DDR, and that mutations of the PARylation sites on TRPS1 lead to i

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11490888 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature