RAD18/YCR066W Summary 
| Standard Name | RAD18 |
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| Systematic Name | YCR066W |
| Feature Type | ORF, Verified |
| Description | E3 ubiquitin ligase; forms heterodimer with Rad6p to monoubiquitinate PCNA-K164; heterodimer binds single-stranded DNA and has single-stranded DNA dependent ATPase activity; required for postreplication repair; SUMO-targeted ubiquitin ligase (STUbl) that contains a SUMO-interacting motif (SIM) which stimulates its ubiquitin ligase activity towards the sumoylated form of PCNA (1, 2, 3 and see Summary Paragraph) |
| Name Description | RADiation sensitive |
| Chromosomal Location | |
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| Genetic position: 67 cM |
| View Computational GO annotations for RAD18 | |
| Molecular Function | |
| Manually curated | |
| Biological Process | |
| Manually curated | |
| Cellular Component | |
| Manually curated |
| 409 total interaction(s) for 186 unique genes/features. | |
| Physical Interactions |
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| Genetic Interactions |
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| Localization | |
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| Phosphorylation | PhosphoGRID | PhosphoPep Database |
| Structure | |
| Homologs |
| This feature contains embedded feature(s): YCRX10W | |||||||||||||
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| Genetic position: 67 cM | |||||||||||||
| Last Update | Coordinates: 2011-02-03 | Sequence: 1997-01-28 | ||||||||||||
| Subfeature details |
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| Retrieve sequences | |||||||||||||
| S288C only | |
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| S288C vs. other species | |
| S288C vs. other strains |
| External Links | All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB |
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| Primary SGDID | S000000662 |
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RAD18 encodes an E3 ubiquitin ligase required for postreplicational DNA repair (PRR) (4 and reviewed in 5). Rad18p promotes replication through DNA lesions located at stalled replication forks through both error-prone and error-free translesion repair. It is a member of the RAD6 epistasis group of DNA repair factors which also includes Rad6p, Rad5p, Mms2p, Ubc13p, Pol30p, Rev1p, Rev3p, Rev7p, and Srs2p (reviewed in 5 and 6).
Rad18p forms a stable heterodimer with Rad6p that possesses ubiquitin conjugating, single-stranded DNA binding, and DNA-dependent ATPase activities (1). Upon DNA damage, Rad6p-Rad18p monoubiquitinates Pol30p (PCNA) at lysine residue 164 to activate translesion repair via polymerases eta (Rad30p) and zeta (Rev3p and Rev7p). Monoubiquitinated PCNA can be subsequently polyubiquitinated in a Rad5p-Mms2p-Ubc13p dependent manner to promote error-free postreplicational repair (7, reviewed in 5).
Rad18p contains both RING finger and zinc finger motifs which are thought to facilitate protein-protein interaction and DNA binding (8, 9). Transcription of RAD18 is induced up to four-fold both by UV irradiation and during meiosis. Increased RAD18 meiotic expression also coincides with peak levels of meiotic recombination (10).
rad18 null mutants are viable but highly sensitive to a broad range of DNA-damaging agents, such as UV and ionizing radiation and alkylating agents (11, 12, 13). RAD18 and its role in postreplication repair is highly conserved and similar genes have been identified in other eukaryotes such as S. pombe, mouse, and human (14, 15, 16).
Last updated: 2006-07-21 
| 1) | Bailly V, et al. (1997) Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has ubiquitin conjugating, DNA binding, and ATP hydrolytic activities. J Biol Chem 272(37):23360-5 |
| 2) | Ulrich HD (2009) Regulating post-translational modifications of the eukaryotic replication clamp PCNA. DNA Repair (Amst) 8(4):461-9 |
| 3) | Parker JL and Ulrich HD (2012) A SUMO-interacting motif activates budding yeast ubiquitin ligase Rad18 towards SUMO-modified PCNA. Nucleic Acids Res 40(22):11380-8 |
| 4) | Jentsch S, et al. (1987) The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 329(6135):131-4 |
| 5) | Prakash S, et al. (2005) Eukaryotic translesion synthesis DNA polymerases: specificity of structure and function. Annu Rev Biochem 74:317-53 |
| 6) | Prakash S, et al. (1993) DNA repair genes and proteins of Saccharomyces cerevisiae. Annu Rev Genet 27:33-70 |
| 7) | Hoege C, et al. (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419(6903):135-41 |
| 8) | Ulrich HD and Jentsch S (2000) Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J 19(13):3388-97 |
| 9) | Jones JS, et al. (1988) The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains potential zinc finger domains for nucleic acid binding and a putative nucleotide binding sequence. Nucleic Acids Res 16(14B):7119-31 |
| 10) | Jones JS and Prakash L (1991) Transcript levels of the Saccharomyces cerevisiae DNA repair gene RAD18 increase in UV irradiated cells and during meiosis but not during the mitotic cell cycle. Nucleic Acids Res 19(4):893-8 |
| 11) | Fabre F, et al. (1989) Isolation of the RAD18 gene of Saccharomyces cerevisiae and construction of rad18 deletion mutants. Mol Gen Genet 215(3):425-30 |
| 12) | Moore CW (1978) Responses of radiation-sensitive mutants of Saccharomyces cerevisiae to lethal effects of bleomycin. Mutat Res 51(2):165-80 |
| 13) | Mowat MR, et al. (1983) Repair of gamma-ray induced DNA strand breaks in the radiation-sensitive mutant rad18-2 of Saccharomyces cerevisiae. Mol Gen Genet 189(2):256-62 |
| 14) | Verkade HM, et al. (2001) A homologue of the Rad18 postreplication repair gene is required for DNA damage responses throughout the fission yeast cell cycle. Mol Genet Genomics 265(6):993-1003 |
| 15) | van der Laan R, et al. (2000) Characterization of mRAD18Sc, a mouse homolog of the yeast postreplication repair gene RAD18. Genomics 69(1):86-94 |
| 16) | Tateishi S, et al. (2000) Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens. Proc Natl Acad Sci U S A 97(14):7927-32 |
