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Mörtl, S. ; Karras, G.I.* ; Wismüller, T. ; Ahne, F. ; Eckardt-Schupp, F.

Regulation of double-stranded DNA gap repair by the RAD6 pathway.

DNA Repair 7, 1893-1906 (2008)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
The RAD6 pathway allows replication across DNA lesions by either an error-prone or error-free mode. Error-prone replication involves translesion polymerases and requires monoubiquitylation at lysine (K) 164 of PCNA by the Rad6 and Rad18 enzymes. By contrast, the error-free bypass is triggered by modification of PCNA by K63-linked polyubiquitin chains, a reaction that requires in addition to Rad6 and Rad18 the enzymes Rad5 and Ubc13-Mms2. Here, we show that the RAD6 pathway is also critical for controlling repair pathways that act on DNA double-strand breaks. By using gapped plasmids as substrates, we found that repair in wild-type cells proceeds almost exclusively by homology-dependent repair (HDR) using chromosomal DNA as a template, whereas non-homologous end-joining (NHEJ) is suppressed. In contrast, in cells deficient in PCNA polyubiquitylation, plasmid repair occurs largely by NHEJ. Mutant cells that are completely deficient in PCNA ubiquitylation, repair plasmids by HDR similar to wild-type cells. These findings are consistent with a model in which unmodified PCNA supports HDR, whereas PCNA monoubiquitylation diverts repair to NHEJ, which is suppressed by PCNA polyubiquitylation. More generally, our data suggest that the balance between HDR and NHEJ pathways is crucially controlled by genes of the RAD6 pathway through modifications of PCNA.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords RAD6 group; DNA double-strand break repair; Ubiquitylation
ISSN (print) / ISBN 1568-7864
e-ISSN 1568-7856
Journal DNA Repair
Quellenangaben Volume: 7, Issue: 11, Pages: 1893-1906 Article Number: , Supplement: ,
Publisher Elsevier
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)