1. PWWP2B promotes DNA end resection and homologous recombination
- Author
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Min Kyung Ju, Joo Rak Lee, Yeonsong Choi, Seon Young Park, Hee Jung Sul, Hee Jin Chung, Soyeong An, Semin Lee, Eunyoung Jung, Bohyun Kim, Bo Youn Choi, Bum Jun Kim, Hyeong Su Kim, Hyun Lim, Ho Suk Kang, Jae Seung Soh, Kyungjae Myung, Kab Choong Kim, Ji Woong Cho, Jinwon Seo, Tae Moon Kim, Ja Yil Lee, Yonghwan Kim, Hongtae Kim, and Dae Young Zang
- Subjects
DNA Repair ,Chromosomal Proteins, Non-Histone ,Ubiquitin-Protein Ligases ,Recombinational DNA Repair ,Articles ,Biochemistry ,Genomic Instability ,Stomach Neoplasms ,CCAAT-Enhancer-Binding Proteins ,Genetics ,Humans ,DNA Breaks, Double-Stranded ,Rad51 Recombinase ,Homologous Recombination ,Molecular Biology ,DNA Damage - 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.
- Published
- 2022