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DC Field | Value | Language |
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dc.citation.number | 9 | - |
dc.citation.startPage | e1002262 | - |
dc.citation.title | PLOS GENETICS | - |
dc.citation.volume | 7 | - |
dc.contributor.author | Hendel, Ayal | - |
dc.contributor.author | Krijger, Peter H. L. | - |
dc.contributor.author | Diamant, Noam | - |
dc.contributor.author | Goren, Zohar | - |
dc.contributor.author | Langerak, Petra | - |
dc.contributor.author | Kim, Jungmin | - |
dc.contributor.author | Reissner, Thomas | - |
dc.contributor.author | Lee, Kyoo-young | - |
dc.contributor.author | Geacintov, Nicholas E. | - |
dc.contributor.author | Carell, Thomas | - |
dc.contributor.author | Myung, Kyungjae | - |
dc.contributor.author | Tateishi, Satoshi | - |
dc.contributor.author | D'Andrea, Alan | - |
dc.contributor.author | Jacobs, Heinz | - |
dc.contributor.author | Livneh, Zvi | - |
dc.date.accessioned | 2023-12-22T05:45:19Z | - |
dc.date.available | 2023-12-22T05:45:19Z | - |
dc.date.created | 2020-01-31 | - |
dc.date.issued | 2011-09 | - |
dc.description.abstract | Translesion DNA synthesis (TLS) is a DNA damage tolerance mechanism in which specialized low-fidelity DNA polymerases bypass replication-blocking lesions, and it is usually associated with mutagenesis. In Saccharomyces cerevisiae a key event in TLS is the monoubiquitination of PCNA, which enables recruitment of the specialized polymerases to the damaged site through their ubiquitin-binding domain. In mammals, however, there is a debate on the requirement for ubiquitinated PCNA (PCNA-Ub) in TLS. We show that UV-induced Rpa foci, indicative of single-stranded DNA (ssDNA) regions caused by UV, accumulate faster and disappear more slowly in Pcna(K164R/K164R) cells, which are resistant to PCNA ubiquitination, compared to Pcna(+/+) cells, consistent with a TLS defect. Direct analysis of TLS in these cells, using gapped plasmids with site-specific lesions, showed that TLS is strongly reduced across UV lesions and the cisplatin-induced intrastrand GG crosslink. A similar effect was obtained in cells lacking Rad18, the E3 ubiquitin ligase which monoubiquitinates PCNA. Consistently, cells lacking Usp1, the enzyme that de-ubiquitinates PCNA exhibited increased TLS across a UV lesion and the cisplatin adduct. In contrast, cells lacking the Rad5-homologs Shprh and Hltf, which polyubiquitinate PCNA, exhibited normal TLS. Knocking down the expression of the TLS genes Rev3L, PolH, or Rev1 in Pcna(K164R/K164R) mouse embryo fibroblasts caused each an increased sensitivity to UV radiation, indicating the existence of TLS pathways that are independent of PCNA-Ub. Taken together these results indicate that PCNA-Ub is required for maximal TLS. However, TLS polymerases can be recruited to damaged DNA also in the absence of PCNA-Ub, and perform TLS, albeit at a significantly lower efficiency and altered mutagenic specificity. | - |
dc.identifier.bibliographicCitation | PLOS GENETICS, v.7, no.9, pp.e1002262 | - |
dc.identifier.doi | 10.1371/journal.pgen.1002262 | - |
dc.identifier.issn | 1553-7404 | - |
dc.identifier.scopusid | 2-s2.0-80053450420 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/31041 | - |
dc.identifier.url | https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002262 | - |
dc.identifier.wosid | 000295419100017 | - |
dc.language | 영어 | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.title | PCNA Ubiquitination Is Important, But Not Essential for Translesion DNA Synthesis in Mammalian Cells | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.type.docType | Article | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | REPAIR | - |
dc.subject.keywordPlus | SUMO | - |
dc.subject.keywordPlus | POLYMERASE-ETA | - |
dc.subject.keywordPlus | 2-POLYMERASE MECHANISMS | - |
dc.subject.keywordPlus | MONOUBIQUITINATED PCNA | - |
dc.subject.keywordPlus | GENOMIC INSTABILITY | - |
dc.subject.keywordPlus | BINDING DOMAINS | - |
dc.subject.keywordPlus | NUCLEAR ANTIGEN | - |
dc.subject.keywordPlus | POL-ETA | - |
dc.subject.keywordPlus | BYPASS | - |
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