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Merck

KRCC1, a modulator of the DNA damage response.

Nucleic acids research (2022-10-17)
Fiifi Neizer-Ashun, Shailendra Kumar Dhar Dwivedi, Anindya Dey, Elangovan Thavathiru, William L Berry, Susan Patricia Lees-Miller, Priyabrata Mukherjee, Resham Bhattacharya
摘要

The lysine-rich coiled-coil 1 (KRCC1) protein is overexpressed in multiple malignancies, including ovarian cancer, and overexpression correlates with poor overall survival. Despite a potential role in cancer progression, the biology of KRCC1 remains elusive. Here, we characterize the biology of KRCC1 and define its role in the DNA damage response and in cell cycle progression. We demonstrate that KRCC1 associates with the checkpoint kinase 1 (CHK1) upon DNA damage and regulates the CHK1-mediated checkpoint. KRCC1 facilitates RAD51 recombinase foci formation and augments homologous recombination repair. Furthermore, KRCC1 is required for proper S-phase progression and subsequent mitotic entry. Our findings uncover a novel component of the DNA damage response and a potential link between cell cycle, associated damage response and DNA repair.

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