Related Researcher

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Myung, Kyungjae
Center for Genomic Integrity
Research Interests
  • DNA Replication, DNA Repair, DNA Recombination, DNA Damage Response, cancer, aging


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

DC Field Value Language Park, Su Hyung ko Kim, Youyoung ko Ra, Jae Sun ko Wie, Min Woo ko Kang, Mi-Sun ko Kang, Sukhyun ko Myung, Kyungjae ko Lee, Kyoo-young ko 2022-01-13T23:53:18Z - 2022-01-10 ko 2021-11 ko
dc.identifier.citation NUCLEIC ACIDS RESEARCH, v.49, no.20, pp.11746 - 11764 ko
dc.identifier.issn 0305-1048 ko
dc.identifier.uri -
dc.description.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. ko
dc.language 영어 ko
dc.publisher OXFORD UNIV PRESS ko
dc.title Timely termination of repair DNA synthesis by ATAD5 is important in oxidative DNA damage-induced single-strand break repair ko
dc.type ARTICLE ko
dc.identifier.scopusid 2-s2.0-85121227645 ko
dc.identifier.wosid 000728384400028 ko
dc.type.rims ART ko
dc.identifier.doi 10.1093/nar/gkab999 ko
dc.identifier.url ko
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