한빛사논문
- 조회431
Min Kyung Ju1,†, Joo Rak Lee1,†, Yeonsong Choi2,†, Seon Young Park3,†, Hee Jung Sul4,†, Hee Jin Chung1, Soyeong An1, Semin Lee2, Eunyoung Jung3, Bohyun Kim4, Bo Youn Choi4, Bum Jun Kim5, Hyeong Su Kim5, Hyun Lim5, Ho Suk Kang5, Jae Seung Soh5, Kyungjae Myung1,6, Kab Choong Kim7, Ji Woong Cho7, Jinwon Seo8, Tae Moon Kim6, Ja Yil Lee1,6, Yonghwan Kim*,3, Hongtae Kim*,1,6 and Dae Young Zang*,4,5
1Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Korea
2Department of Biomedical Engineering, Ulsan National Institute of Science and Technology, Ulsan, Korea
3Department of Biological Sciences, Research Institute of Women’s Health, Sookmyung Women's University, Seoul, Korea
4Hallym Translational Research Institute, Hallym University Sacred Heart Hospital, Anyang-si, Korea
5Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Korea
6Center for Genomic Integrity Institute for Basic Science (IBS), Ulsan, Korea
7Department of Surgery, Hallym University Medical Center, Hallym University College of Medicine, Anyang-si, Korea
8Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Korea
† These authors contributed equally to this work
*Corresponding author.
Abstract
Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.
논문정보
- Research article
- 2022년 05월 (BRIC 등록일 2022-05-27)
- 국내 연구진
- 의약학 > 응용의학
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