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KRCC1, a modulator of the DNA damage response.

Fiifi Neizer-AshunShailendra Kumar Dhar DwivediAnindya DeyElangovan ThavathiruWilliam L BerrySusan Patricia Lees-MillerPriyabrata MukherjeeResham Bhattacharya
Published in: Nucleic acids research (2022)
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.
Keyphrases
  • dna damage response
  • dna repair
  • cell cycle
  • dna damage
  • cell proliferation
  • oxidative stress
  • papillary thyroid
  • transcription factor
  • squamous cell carcinoma
  • tyrosine kinase
  • amino acid
  • lymph node metastasis