The DNA replication machinery stalls at damaged sites on DNA. Postreplicaton repair (PRR) is a system to avoid cell death in such circumstances of deadlock. In Saccharomyces cerevisiae, the Rad6/Rad18 heterodimer plays pivotal roles in PRR. It promotes translesion synthesis via the monoubiquitylation of the DNA sliding clamp, PCNA. Ubc13/Mms2/Rad5 can extend the ubiquitin chain from this monoubiquitylated PCNA with a non-canonical lysine 63-linked ubiquitin-chain, resulting in an error-free mode of bypass. In this study, we identified and characterized the RAD5 homolog in Neurospora crassa, which we named mus-41. A mus-41 mutant was sensitive to several DNA-damaging agents including UV and MMS. Genetic analyses indicated that uvs-2 (RAD18 homolog) was epistatic to mus-41, suggesting a role for mus-41 in postreplication repair. Additionally, it was shown that mus-41 has a role independent from TLS gene upr-1 (REV3 homolog) and works in the error-free pathway, indicating that the function of mus-41 as a RAD5 homolog is also conserved in N. crassa. However, mus-41 is not essential for the ubiquitylation of PCNA that is detected in the wild-type background, suggesting that there is another ubiquitin ligase catalyzing ubiquitylation of PCNA in response to UV in N. crassa.

• PMID: 17703305
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Kawabata T, Kato A, Suzuki K, Inoue H

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