title: Neurosprora crassa RAD5 homologue, mus-41, inactivation results in higher sensitivity to mutagens but has little effect on PCNA-ubiquitylation in response to UV-irradiation.
abstract: 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.
authors: Department of Regulation Biology, Saitama University, Sakura-ku Shimo-ookubo 255, Saitama city, Saitama 338-8570, Japan. hinoue@post.saitama-u.ac.jp
authors: Tsuyoshi
authors: T
authors: Kawabata
authors: Akihiro
authors: A
authors: Kato
authors: Keiichiro
authors: K
authors: Suzuki
authors: Hirokazu
authors: H
authors: Inoue
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology*; D009492:Neurospora crassa / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D005656:Fungal Proteins; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; D025801:Ubiquitin; D008741:Methyl Methanesulfonate; D044763:Ubiquitin-Conjugating Enzymes; D000251:Adenosine Triphosphatases
references: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15954-9
references: 16247017
references: Mol Cell Biol. 2003 Jan;23(2):474-81
references: 12509447
references: EMBO J. 2004 Oct 1;23(19):3886-96
references: 15359278
references: Genetics. 2006 Jan;172(1):113-25
references: 16219790
references: Nature. 2003 Sep 11;425(6954):188-91
references: 12968183
references: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10352-10357
references: 16801547
references: Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18107-12
references: 17108083
references: Genetics. 2005 Feb;169(2):575-82
references: 15520252
references: Nucleic Acids Res. 1993 Dec 25;21(25):5964-71
references: 8290359
references: Annu Rev Biochem. 2005;74:317-53
references: 15952890
references: Nucleic Acids Res. 2005 Mar 30;33(6):1848-58
references: 15800214
references: Curr Genet. 1996 Aug;30(3):224-31
references: 8753651
references: EMBO J. 2002 Oct 15;21(20):5558-66
references: 12374756
references: Mol Biol Cell. 2006 Jul;17(7):2976-85
references: 16641370
references: Proc Natl Acad Sci U S A. 1986 Jul;83(13):4869-73
references: 16593723
references: J Biol Chem. 1997 Sep 12;272(37):23360-5
references: 9287349
references: Nucleic Acids Res. 2007;35(3):881-9
references: 17251197
references: J Cell Biol. 2006 Dec 4;175(5):703-8
references: 17130289
references: Mol Cell Biol. 1992 Sep;12(9):3807-18
references: 1324406
references: Mol Genet Genomics. 2002 May;267(3):401-8
references: 12073042
references: Fungal Genet Biol. 1999 Oct;28(1):12-20
references: 10512668
references: Nature. 2002 Sep 12;419(6903):135-41
references: 12226657
references: Mol Gen Genet. 1993 Apr;238(1-2):225-33
references: 8097557
references: Mol Cell Biol. 2006 Feb;26(4):1424-33
references: 16449653
references: Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12248-53
references: 15299145
references: Nucleic Acids Res. 2000 Jul 15;28(14):2847-54
references: 10908344
references: Cell. 1987 Dec 4;51(5):741-52
references: 2960455
references: Mutat Res. 1980 Jul;71(2):181-91
references: 6446682
references: Mol Gen Genet. 1997 Oct;256(4):436-45
references: 9393441
references: Mutat Res. 1998 Sep 11;408(3):171-82
references: 9806416
references: Mol Cell. 2004 May 21;14(4):491-500
references: 15149598
references: Mutat Res. 1984 Feb;125(2):185-94
references: 6230534
references: EMBO Rep. 2006 Sep;7(9):927-32
references: 16888649
references: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7927-32
references: 10884424
references: Mol Cell Biol. 1997 Aug;17(8):4536-43
references: 9234711