KRCC1, a modulator of the DNA damage response

• Published in: Nucleic acids research 2022-10, Vol.50 (19), p.11028-11039
• Main Authors: Neizer-Ashun, Fiifi, Dwivedi, Shailendra Kumar Dhar, Dey, Anindya, Thavathiru, Elangovan, Berry, William L, Lees-Miller, Susan Patricia, Mukherjee, Priyabrata, Bhattacharya, Resham
• Format: Article
• Language: English
• Subjects: Checkpoint Kinase 1 - genetics; Checkpoint Kinase 1 - metabolism; DNA Damage; DNA Repair; Genome Integrity, Repair and; Protein Kinases - genetics; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; Recombinational DNA Repair
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkac890

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.