RAD18/YCR066W Summary Help

Standard Name RAD18
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
ChrIII:231500 to 232963 | ORF Map | GBrowse
Gbrowse
Genetic position: 67 cM
Gene Ontology Annotations All RAD18 GO evidence and references
  View Computational GO annotations for RAD18
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 1 genes
Resources
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
Resources
419 total interaction(s) for 188 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 7
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 15
  • Biochemical Activity: 6
  • Co-localization: 1
  • Far Western: 3
  • Reconstituted Complex: 6
  • Two-hybrid: 31

Genetic Interactions
  • Dosage Rescue: 1
  • Negative Genetic: 79
  • Phenotypic Enhancement: 34
  • Phenotypic Suppression: 17
  • Positive Genetic: 8
  • Synthetic Growth Defect: 160
  • Synthetic Lethality: 13
  • Synthetic Rescue: 36

Resources
Expression Summary
histogram
Resources
Length (a.a.) 487
Molecular Weight (Da) 55,230
Isoelectric Point (pI) 7.55
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIII:231500 to 232963 | ORF Map | GBrowse
This feature contains embedded feature(s): YCRX10W
SGD ORF map
Genetic position: 67 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1464 231500..232963 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000662
SUMMARY PARAGRAPH for RAD18

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 Contact SGD

References cited on this page View Complete Literature Guide for RAD18
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