Roles of the SUMO-related enzymes, PIAS1, PIAS4, and RNF4, in DNA double-strand break repair by homologous recombination

• Material Type: 博士論文
• Title: Roles of the SUMO-related enzymes, PIAS1, PIAS4, and RNF4, in DNA double-strand break repair by homologous recombination
• Author/Editor: HAN, MOE MOE
• Author Heading: HAN, MOE MOE
• Publication, Distribution, etc.: Elsevier Inc.
• Publication Date: 2022-03-18
• Publication Date (W3CDTF): 2022-03-18
• Alternative Title: SUMO関連酵素PIAS1、PIAS4及びRNF4のDNA二本鎖切断相同組換え修復における役割
• Periodical title: Biochemical and Biophysical Research Communications
• No. or year of volume/issue: 591
• Volume: 591
• Pages: 95-
• ISSN (Periodical Title): ISSN : 0006-291X
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2022-03-18
• Dissertation Number: 甲医歯薬第1445号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: DNA double-strand break; Homologous recombination; Resection; Small ubiquitin-like modifier
• Target Audience: 一般
• Note (General): Post-translational modification of proteins by small ubiquitin-like modifier (SUMO) is known to be involved in a variety of cellular events. This modification, called SUMOylation, is carried out by the E1 activating enzyme, the E2 conjugating enzyme, and multiple E3 ligases. Previous studies have demonstrated that the SUMO E3 ligases, protein inhibitors of activated STAT 1 (PIAS1) and 4 (PIAS4), and the SUMO-targeted ubiquitin ligase, RING finger protein 4 (RNF4), play important roles in the repair of DNA double-strand breaks (DSBs). However, the mechanism by which these SUMO-related enzymes promote DSB repair is still poorly understood. In the present study, we focused on homologous recombination (HR), the most accurate DSB repair pathway, and aimed to elucidate the mechanism by which PIAS1, PIAS4, and RNF4 promote HR. In γ-ray-irradiated normal human fibroblasts, DSB end resection and RAD51 loading, the two essential steps of HR, were significantly impaired by small interfering RNA (siRNA)-mediated depletion of PIAS1, PIAS4, or RNF4. The recruitment of BRCA1, a major HR factor, to DSB sites was reduced in cells depleted of these SUMO-related enzymes. Consistent with the role of BRCA1 in counteracting the p53-binding protein 1 (53BP1)-mediated resection blockade, 53BP1 depletion rescued the reduced resection and RAD51 loading in the cells depleted of PIAS1, PIAS4, or RNF4. Moreover, Rap1-interacting factor 1 (RIF1), a resection inhibitor downstream of 53BP1, became more abundant at DSBs when PIAS1, PIAS4, RNF4, or BRCA1 was depleted. Importantly, the concomitant depletion of BRCA1 with either one of the SUMO-related enzymes did not further increase RIF1 at DSBs, when compared to single depletion of BRCA1. Collectively, these results suggest that PIAS1, PIAS4, RNF4, and BRCA1 work epistatically to counteract 53BP1/RIF1-mediated resection blockade, thereby promoting resection.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1445号 学位授与年月日:令和4年3月18日; Author: Moe Moe Han, Miyako Hirakawa, Motohiro Yamauchi, Naoki Matsuda; Citation: Biochemical and Biophysical Research Communications, 591, pp. 95-101; 2022; identifier:Nagasaki University (長崎大学), 博士(医学) (2022-03-18)
• Source: https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27428&item_no=1&attribute_id=70&file_no=1 （fulltext）; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27428&item_no=1&attribute_id=70&file_no=1
• Access Restrictions: インターネット公開
• Rights (production): © 2021 Elsevier Inc. All rights reserved.
• Related Material: http://hdl.handle.net/10069/00041448
• Related Material (DOI): 10.1016/j.bbrc.2021.12.099
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ