BROWSE

Related Scientist

Su Hyung, Park's photo.

Su Hyung, Park
유전체 항상성 연구단
more info

ITEM VIEW & DOWNLOAD

Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair

Cited 0 time in webofscience Cited 0 time in scopus
315 Viewed 0 Downloaded
Title
Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair
Author(s)
Su Hyung Park; Youyoung Kim; Jae Sun Ra; Min woo Wie; Mi Sun Kang; Sukhyun Kang; Kyung Jae Myung; Kyoo Young Lee
Publication Date
2021-11
Journal
Nucleic Acids Research, v.49, no.20, pp.11746 - 11764
Publisher
Oxford University Press
Abstract
Abstract Reactive oxygen species (ROS) generate oxidized bases and single-strand breaks (SSBs), which are fixed by base excision repair (BER) and SSB repair (SSBR), respectively. Although excision and repair of damaged bases have been extensively studied, the function of the sliding clamp, proliferating cell nuclear antigen (PCNA), including loading/unloading, remains unclear. We report that, in addition to PCNA loading by replication factor complex C (RFC), timely PCNA unloading by the ATPase family AAA domain-containing protein 5 (ATAD5)-RFC–like complex is important for the repair of ROS-induced SSBs. We found that PCNA was loaded at hydrogen peroxide (H2O2)-generated direct SSBs after the 3′-terminus was converted to the hydroxyl moiety by end-processing enzymes. However, PCNA loading rarely occurred during BER of oxidized or alkylated bases. ATAD5-depleted cells were sensitive to acute H2O2 treatment but not methyl methanesulfonate treatment. Unexpectedly, when PCNA remained on DNA as a result of ATAD5 depletion, H2O2-induced repair DNA synthesis increased in cancerous and normal cells. Based on higher H2O2-induced DNA breakage and SSBR protein enrichment by ATAD5 depletion, we propose that extended repair DNA synthesis increases the likelihood of DNA polymerase stalling, shown by increased PCNA monoubiquitination, and consequently, harmful nick structures are more frequent.
URI
https://pr.ibs.re.kr/handle/8788114/11761
DOI
10.1093/nar/gkab999
ISSN
0305-1048
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
Files in This Item:
There are no files associated with this item.

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse