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Lee, Ja Yil
Biochemistry and Molecular Biophysics
Research Interests
  • DNA damage repair and chromatin dynamics

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PWWP2B promotes DNA end resection and homologous recombination

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Title
PWWP2B promotes DNA end resection and homologous recombination
Author
Ju, Min KyungLee, Joo RakChoi, YeonsongPark, Seon YoungSul, Hee JungChung, Hee JinAn, SoyeongLee, SeminJung, EungyoungKim, BohyunChoi, Bo YounKim, Bum JunKim, Heong SuLim, HyunKang, Ho SukSoh, Jae SeungMyung, KyungjaeKim, Kab ChoongCho, Ji WoongSeo, JinwonKim, Tae MoonLee, Ja YilKim, YonghwanKim, HongtaeZang, Dae Young
Issue Date
2022-07
Publisher
WILEY
Citation
EMBO REPORTS, v.23, no.7, pp.e53492
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.
URI
https://scholarworks.unist.ac.kr/handle/201301/58561
URL
https://www.embopress.org/doi/full/10.15252/embr.202153492
DOI
10.15252/embr.202153492
ISSN
1469-221X
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BIO_Journal Papers
BME_Journal Papers
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