KRCC1, a modulator of the DNA damage response-Reference-Cited by-同舟云学术

KRCC1, a modulator of the DNA damage response

Published:2022-10-16 Issue:19 Volume:50 Page:11028-11039
ISSN:0305-1048
Container-title:Nucleic Acids Research
language:en
Short-container-title:

Author:

Neizer-Ashun Fiifi¹,Dwivedi Shailendra Kumar Dhar²,Dey Anindya²,Thavathiru Elangovan²,Berry William L³⁴,Lees-Miller Susan Patricia⁵,Mukherjee Priyabrata⁴⁶,Bhattacharya Resham¹²⁴^ORCID

Affiliation:

1. Department of Cell Biology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104, USA

2. Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104, USA

3. Department of Surgery, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104, USA

4. Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104, USA

5. Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary , Calgary, Alberta, T2N 4N1, Canada

6. Department of Pathology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104, USA

Abstract

Abstract 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.

Funder

Oklahoma Center for Adult Stem Cell Research - a program of TSET

U.S. Department of Defense

National Cancer Institute

Publisher

Oxford University Press (OUP)

Subject

Genetics

Link

https://academic.oup.com/nar/article-pdf/50/19/11028/46844013/gkac890.pdf

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