KRCC1, a modulator of the DNA damage response

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 KRCC...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkac890