이규영 (기초과학연구원, 한림대학교 의과대학)

한빛사논문

조회642

기초과학연구원, 한림대학교 의과대학

CV File 117 kb

Nucleic Acids Res., Sep 22 2023, gkad776 | https://doi.org/10.1093/nar/gkad776 Short-range end resection requires ATAD5-mediated PCNA unloading for faithful homologous recombination.

Su Hyung Park ^1,2, Namwoo Kim ^1,3, Nalae Kang ¹, Eunjin Ryu ^1,3, Eun A Lee ¹, Jae Sun Ra ¹, Anton Gartner ^1,3, Sukhyun Kang ¹, Kyungjae Myung ^1,2, Kyoo-Young Lee^1,4

¹Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Korea.

²Department of Biomedical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.

³Department of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea.

⁴Department of Biochemistry, College of Medicine, Hallym University, Chuncheon 24252, Korea.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.

To whom correspondence should be addressed. : Kyoo-Young Lee

Abstract

Homologous recombination (HR) requires bidirectional end resection initiated by a nick formed close to a DNA double-strand break (DSB), dysregulation favoring error-prone DNA end-joining pathways. Here we investigate the role of the ATAD5, a PCNA unloading protein, in short-range end resection, long-range resection not being affected by ATAD5 deficiency. Rapid PCNA loading onto DNA at DSB sites depends on the RFC PCNA loader complex and MRE11-RAD50-NBS1 nuclease complexes bound to CtIP. Based on our cytological analyses and on an in vitro system for short-range end resection, we propose that PCNA unloading by ATAD5 is required for the completion of short-range resection. Hampering PCNA unloading also leads to failure to remove the KU70/80 complex from the termini of DSBs hindering DNA repair synthesis and the completion of HR. In line with this model, ATAD5-depleted cells are defective for HR, show increased sensitivity to camptothecin, a drug forming protein-DNA adducts, and an augmented dependency on end-joining pathways. Our study highlights the importance of PCNA regulation at DSB for proper end resection and HR.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-25)
연구진국내 연구진
분야 생명과학 > 분자생물학

댓글 작성 로그인

CV 열람하기

연락처 보기