Genomes and Genes
Gene Symbol: RAD18
Description: E3 ubiquitin-protein ligase RAD18
Alias: E3 ubiquitin-protein ligase RAD18
Species: Saccharomyces cerevisiae S288c
- Colavito S, Macris Kiss M, Seong C, Gleeson O, Greene E, Klein H, et al. Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption. Nucleic Acids Res. 2009;37:6754-64 pubmed publisher..These results highlight the importance of Rad51 interaction in the anti-recombinase function of Srs2, and provide evidence that this Srs2 function can be uncoupled from its helicase activity. ..
- Branzei D, Vanoli F, Foiani M. SUMOylation regulates Rad18-mediated template switch. Nature. 2008;456:915-20 pubmed publisher..Gap-filling repair requires homologous recombination as well as Rad18- and Rad5-mediated proliferating cell nuclear antigen (PCNA) polyubiquitylation...
- Motegi A, Kuntz K, Majeed A, Smith S, Myung K. Regulation of gross chromosomal rearrangements by ubiquitin and SUMO ligases in Saccharomyces cerevisiae. Mol Cell Biol. 2006;26:1424-33 pubmed..Previously, we showed that inactivation of Rad5 or Rad18, ubiquitin ligases (E3) targeting for proliferating cell nuclear antigen (PCNA), increases the de novo telomere ..
- Northam M, Garg P, Baitin D, Burgers P, Shcherbakova P. A novel function of DNA polymerase zeta regulated by PCNA. EMBO J. 2006;25:4316-25 pubmed..of a PCNA mutant defective for functional interactions with Polzeta, but not for monoubiquitination by the Rad6/Rad18 complex demonstrate a role for PCNA in regulating the mutagenic activity of Polzeta separate from its modification ..
- Kats E, Enserink J, Martinez S, Kolodner R. The Saccharomyces cerevisiae Rad6 postreplication repair and Siz1/Srs2 homologous recombination-inhibiting pathways process DNA damage that arises in asf1 mutants. Mol Cell Biol. 2009;29:5226-37 pubmed publisher..Our results show that ASF1 probably contributes to the maintenance of genome stability through multiple mechanisms, some of which involve the PRR and HRS pathways...
- Vijeh Motlagh N, Seki M, Branzei D, Enomoto T. Mgs1 and Rad18/Rad5/Mms2 are required for survival of Saccharomyces cerevisiae mutants with novel temperature/cold sensitive alleles of the DNA polymerase delta subunit, Pol31. DNA Repair (Amst). 2006;5:1459-74 pubmed..Surprisingly, deletions of RAD18 and MGS1 aggravated the temperature sensitivity conferred by most ts or cs alleles and specifically suppressed the ..
- Daee D, Mertz T, Lahue R. Postreplication repair inhibits CAG.CTG repeat expansions in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:102-10 pubmed..Like srs2 mutants, expansions are elevated in rad18 and rad5 mutants, as well as the PRR-specific PCNA alleles pol30-K164R and pol30-K127/164R...
- Friedl A, Liefshitz B, Steinlauf R, Kupiec M. Deletion of the SRS2 gene suppresses elevated recombination and DNA damage sensitivity in rad5 and rad18 mutants of Saccharomyces cerevisiae. Mutat Res. 2001;486:137-46 pubmedThe Saccharomyces cerevisiae genes RAD5, RAD18, and SRS2 are proposed to act in post-replicational repair of DNA damage...
- Xiao W, Chow B, Broomfield S, Hanna M. The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways. Genetics. 2000;155:1633-41 pubmed..mutations in each of the three subpathways are phenotypically indistinguishable from a single mutant such as rad18, which is defective in the entire RAD6 postreplication repair/tolerance pathway...
- Branzei D, Seki M, Onoda F, Enomoto T. The product of Saccharomyces cerevisiae WHIP/MGS1, a gene related to replication factor C genes, interacts functionally with DNA polymerase delta. Mol Genet Genomics. 2002;268:371-86 pubmed..Possible roles of Mgs1, DNA polymerase delta, Rad18 and Mms2 in replication and replication fork restart are discussed.
- Hoege C, Pfander B, Moldovan G, Pyrowolakis G, Jentsch S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature. 2002;419:135-41 pubmed..enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING-finger proteins RAD18 and RAD5, respectively...
- Windecker H, Ulrich H. Architecture and assembly of poly-SUMO chains on PCNA in Saccharomyces cerevisiae. J Mol Biol. 2008;376:221-31 pubmed
- Pfander B, Moldovan G, Sacher M, Hoege C, Jentsch S. SUMO-modified PCNA recruits Srs2 to prevent recombination during S phase. Nature. 2005;436:428-33 pubmed..Our finding suggests a model in which SUMO-modified PCNA recruits Srs2 in S phase in order to prevent unwanted recombination events of replicating chromosomes. ..
- Haracska L, Unk I, Prakash L, Prakash S. Ubiquitylation of yeast proliferating cell nuclear antigen and its implications for translesion DNA synthesis. Proc Natl Acad Sci U S A. 2006;103:6477-82 pubmedThe Rad6-Rad18 ubiquitin-conjugating enzyme complex promotes replication through DNA lesions by means of at least three different pathways: the DNA polymerase (Pol) eta- and zeta-dependent translesion DNA synthesis (TLS) and a Rad5-Mms2-..
- de Padula M, Slezak G, Auffret van Der Kemp P, Boiteux S. The post-replication repair RAD18 and RAD6 genes are involved in the prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae. Nucleic Acids Res. 2004;32:5003-10 pubmed..In the present study, we show the RAD18 and RAD6 genes that are required to initiate post-replication repair (PRR) are also involved in the prevention of ..
- Broomfield S, Chow B, Xiao W. MMS2, encoding a ubiquitin-conjugating-enzyme-like protein, is a member of the yeast error-free postreplication repair pathway. Proc Natl Acad Sci U S A. 1998;95:5678-83 pubmed..The rad6 and rad18 mutants are defective in both pathways, and the rev3 mutant affects only the mutagenesis pathway, but a yeast gene ..
- Chen C, Motegi A, Hasegawa Y, Myung K, Kolodner R, D ANDREA A. Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164 SUMOylation and ubiquitination. DNA Repair (Amst). 2006;5:1475-88 pubmed..Further analysis of a mutant simultaneously defective in SUMOylation and mono-ubiquitination (rad18 siz1) revealed that these modifications redundantly affected TLS as well as NHEJ...
- Davies A, Huttner D, Daigaku Y, Chen S, Ulrich H. Activation of ubiquitin-dependent DNA damage bypass is mediated by replication protein a. Mol Cell. 2008;29:625-36 pubmed publisher..We found that RPA directly interacts with the ubiquitin ligase responsible for the modification of PCNA, Rad18, both in yeast and in mammalian cells...
- Armstrong A, Mohideen F, Lima C. Recognition of SUMO-modified PCNA requires tandem receptor motifs in Srs2. Nature. 2012;483:59-63 pubmed publisher..The mechanism presented is pertinent to understanding how other receptors specifically recognize Ub- and Ubl-modified substrates to facilitate signal transduction. ..
- Ulrich H. The srs2 suppressor of UV sensitivity acts specifically on the RAD5- and MMS2-dependent branch of the RAD6 pathway. Nucleic Acids Res. 2001;29:3487-94 pubmed..Loss-of-function mutations in srs2 suppress the extreme sensitivity towards UV radiation of rad6 and rad18 mutants, both of which are impaired in post-replication DNA repair and damage-induced mutagenesis...
- Le Breton C, Dupaigne P, Robert T, Le Cam E, Gangloff S, Fabre F, et al. Srs2 removes deadly recombination intermediates independently of its interaction with SUMO-modified PCNA. Nucleic Acids Res. 2008;36:4964-74 pubmed publisher..In addition, crossover (CO) frequencies are increased in both mutants. The different roles of Srs2, in relation to its eventual recruitment by sumoylated PCNA, are discussed. ..
- McDonald J, Levine A, Woodgate R. The Saccharomyces cerevisiae RAD30 gene, a homologue of Escherichia coli dinB and umuC, is DNA damage inducible and functions in a novel error-free postreplication repair mechanism. Genetics. 1997;147:1557-68 pubmed..However, unlike rev mutants, no defect in UV-induced reversion was seen in rad30 strains. While rad6 and rad18 are both epistatic to rad30, no epistasis was observed with rev1, rev3, rev7 or rad5, all of which are members of ..
- Stelter P, Ulrich H. Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature. 2003;425:188-91 pubmed..Our findings assign a function to SUMO during S phase and demonstrate how ubiquitin and SUMO, by regulating the accuracy of replication and repair, contribute to overall genomic stability. ..
- Fu Y, Zhu Y, Zhang K, Yeung M, Durocher D, Xiao W. Rad6-Rad18 mediates a eukaryotic SOS response by ubiquitinating the 9-1-1 checkpoint clamp. Cell. 2008;133:601-11 pubmed publisher..Here, we demonstrate that the ubiquitination complex Rad6-Rad18 is required for the increased transcription of a large number of yeast genes in response to DNA damage...
- Karras G, Jentsch S. The RAD6 DNA damage tolerance pathway operates uncoupled from the replication fork and is functional beyond S phase. Cell. 2010;141:255-67 pubmed publisher..We therefore propose that the RAD6 pathway acts on single-stranded gaps left behind newly restarted replication forks. ..
- Parker J, Ulrich H. Mechanistic analysis of PCNA poly-ubiquitylation by the ubiquitin protein ligases Rad18 and Rad5. EMBO J. 2009;28:3657-66 pubmed publisher..analysed the mechanism of poly-ubiquitylation of the replication clamp PCNA by two cooperating E2-E3 pairs, Rad6-Rad18 and Ubc13-Mms2-Rad5...
- Parker J, Bucceri A, Davies A, Heidrich K, Windecker H, Ulrich H. SUMO modification of PCNA is controlled by DNA. EMBO J. 2008;27:2422-31 pubmed publisher..Instead, the stimulatory effect of DNA on conjugation is mainly attributable to DNA binding of PCNA itself. These findings imply a change in the properties of PCNA upon loading that enhances its capacity to be sumoylated. ..
- Xiao W, Chow B, Rathgeber L. The repair of DNA methylation damage in Saccharomyces cerevisiae. Curr Genet. 1996;30:461-8 pubmed..We found that cells carrying rad6, rad18, rad50 and rad52 single mutations are far more sensitive to killing by MMS than the mag1 mutant, that double ..
- Rong L, Palladino F, Aguilera A, Klein H. The hyper-gene conversion hpr5-1 mutation of Saccharomyces cerevisiae is an allele of the SRS2/RADH gene. Genetics. 1991;127:75-85 pubmed..This mutation suppresses the UV sensitive phenotype of rad18 mutations in hpr5-1 rad18 double mutants by channeling the aborted repair events into a recombination repair ..
- Papouli E, Chen S, Davies A, Huttner D, Krejci L, Sung P, et al. Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p. Mol Cell. 2005;19:123-33 pubmed..Our findings suggest a mechanism by which SUMO and ubiquitin cooperatively control the choice of pathway for the processing of DNA lesions during replication. ..
- Kolesar P, Sarangi P, Altmannova V, Zhao X, Krejci L. Dual roles of the SUMO-interacting motif in the regulation of Srs2 sumoylation. Nucleic Acids Res. 2012;40:7831-43 pubmed publisher..Our findings suggest a potential mechanism for the equilibrium of sumoylated and PCNA-bound pools of Srs2 in cells. ..
- Chen S, Davies A, Sagan D, Ulrich H. The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner. Nucleic Acids Res. 2005;33:5878-86 pubmed
- Hishida T, Ohno T, Iwasaki H, Shinagawa H. Saccharomyces cerevisiae MGS1 is essential in strains deficient in the RAD6-dependent DNA damage tolerance pathway. EMBO J. 2002;21:2019-29 pubmed..We found that mgs1 is synthetic lethal with rad6 and exhibits a synergistic growth defect with rad18 and rad5, which are members of the RAD6 epistasis group important for tolerance of DNA damage during DNA ..
- Huang M, Rio A, Galibert M, Galibert F. Pol32, a subunit of Saccharomyces cerevisiae DNA polymerase delta, suppresses genomic deletions and is involved in the mutagenic bypass pathway. Genetics. 2002;160:1409-22 pubmed..Taken together, these observations indicate that Pol32 is important in ensuring genome stability and in mutagenesis. ..
- Saugar I, Parker J, Zhao S, Ulrich H. The genome maintenance factor Mgs1 is targeted to sites of replication stress by ubiquitylated PCNA. Nucleic Acids Res. 2012;40:245-57 pubmed publisher..Our identification of Mgs1 as a UBZ-dependent downstream effector of ubiquitylated PCNA suggests an explanation for the ambivalent role of the protein in damage processing. ..
- Bailly V, Lamb J, Sung P, Prakash S, Prakash L. Specific complex formation between yeast RAD6 and RAD18 proteins: a potential mechanism for targeting RAD6 ubiquitin-conjugating activity to DNA damage sites. Genes Dev. 1994;8:811-20 pubmed..Here, we show that RAD6 forms a specific complex with the product of the DNA repair gene RAD18. The biological significance of this interaction is attested by the observation that overproduction of the rad6 ..
- Giot L, Chanet R, Simon M, Facca C, Faye G. Involvement of the yeast DNA polymerase delta in DNA repair in vivo. Genetics. 1997;146:1239-51 pubmed..SDP5 is most probably the p55 subunit of Pol delta of S. cerevisiae and seems to be associated with the catalytic subunit for both DNA replication and DNA repair. ..
- Hwang J, Smith S, Myung K. The Rad1-Rad10 complex promotes the production of gross chromosomal rearrangements from spontaneous DNA damage in Saccharomyces cerevisiae. Genetics. 2005;169:1927-37 pubmed..Results presented here suggest that Rad1-Rad10 functions at different stages of GCR formation and that there is an alternative pathway for the GCR formation that is independent of Rad1-Rad10. ..
- Huang D, Piening B, Paulovich A. The preference for error-free or error-prone postreplication repair in Saccharomyces cerevisiae exposed to low-dose methyl methanesulfonate is cell cycle dependent. Mol Cell Biol. 2013;33:1515-27 pubmed publisher..We show that upon exposure to low-dose MMS, a PRR-defective rad18? mutant stalls into a lengthy G2 arrest associated with the accumulation of single-stranded DNA (ssDNA) gaps...
- Putnam C, Hayes T, Kolodner R. Post-replication repair suppresses duplication-mediated genome instability. PLoS Genet. 2010;6:e1000933 pubmed publisher..Here, we found that the RAD6- and RAD18-dependent post-replication repair (PRR) and the RAD5-, MMS2-, UBC13-dependent error-free PRR branch acted in ..
- Xue C, Liang K, Liu Z, Wen R, Xiao W. Similarities and differences between Arabidopsis PCNA1 and PCNA2 in complementing the yeast DNA damage tolerance defect. DNA Repair (Amst). 2015;28:28-36 pubmed publisher..Collectively, it is concluded that the two AtPCNAs differ in their efficiency for ubiquitination and sumoylation, leading to their differential responses to DNA damage in yeast cells. ..
- McIntyre J, Podlaska A, Skoneczna A, Halas A, Sledziewska Gojska E. Analysis of the spontaneous mutator phenotype associated with 20S proteasome deficiency in S. cerevisiae. Mutat Res. 2006;593:153-63 pubmed..occurring spontaneously in yeast cells deficient in 20S proteasome function are connected with the unique Rad6/Rad18-dependent error-prone translesion DNA synthesis (TLS) requiring the activities of both TLS polymerases: Pol eta ..
- Kiakos K, Sato A, Asao T, McHugh P, Lee M, Hartley J. DNA sequence selective adenine alkylation, mechanism of adduct repair, and in vivo antitumor activity of the novel achiral seco-amino-cyclopropylbenz[e]indolone analogue of duocarmycin AS-I-145. Mol Cancer Ther. 2007;6:2708-18 pubmed..adduct elimination occurred in a transcription-coupled manner and was dependent on a functional NER pathway and Rad18. The involvement of NER as the predominant excision pathway was confirmed in mammalian DNA repair mutant cells...
- Game J, Williamson M, Spicakova T, Brown J. The RAD6/BRE1 histone modification pathway in Saccharomyces confers radiation resistance through a RAD51-dependent process that is independent of RAD18. Genetics. 2006;173:1951-68 pubmed..We conclude that IR resistance conferred by BRE1 and DOT1 is mediated through homologous recombinational repair, not postreplication repair, and confirm findings of a G1 checkpoint role for the RAD6/BRE1/DOT1 pathway. ..
- Hanway D, Chin J, Xia G, Oshiro G, Winzeler E, Romesberg F. Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast. Proc Natl Acad Sci U S A. 2002;99:10605-10 pubmed..Epistatsis analysis of four of the genes was performed to determine the DNA damage repair pathways in which the protein products function. ..
- Eckardt Schupp F, Siede W, Game J. The RAD24 (= Rs1) gene product of Saccharomyces cerevisiae participates in two different pathways of DNA repair. Genetics. 1987;115:83-90 pubmed..Properties of the mutant are discussed which hint at the control of late steps in the pathways. ..
- Liu J, Ede C, Wright W, Gore S, Jenkins S, Freudenthal B, et al. Srs2 promotes synthesis-dependent strand annealing by disrupting DNA polymerase Î´-extending D-loops. elife. 2017;6: pubmed publisher..Our data establish a biochemical mechanism for the role of Srs2 in crossover suppression by promoting SDSA through disruption of extended D-loops. ..
- Pastushok L, Hanna M, Xiao W. Constitutive fusion of ubiquitin to PCNA provides DNA damage tolerance independent of translesion polymerase activities. Nucleic Acids Res. 2010;38:5047-58 pubmed publisher..As expected, the DNA damage resistance provided by PCNA.Ub is not dependent on RAD18 or UBC13. Surprisingly, inactivation of TLS polymerases did not abolish PCNA...
- Parker J, Ulrich H. SIM-dependent enhancement of substrate-specific SUMOylation by a ubiquitin ligase in vitro. Biochem J. 2014;457:435-40 pubmed publisher..In ubiquitin ligase Rad18 (radiation-sensitive 18) from Saccharomyces cerevisiae, a SIM, contributes to the recognition of SUMOylated PCNA (..
- Minesinger B, Jinks Robertson S. Roles of RAD6 epistasis group members in spontaneous polzeta-dependent translesion synthesis in Saccharomyces cerevisiae. Genetics. 2005;169:1939-55 pubmed..data are consistent with a model in which Polzeta-dependent mutagenesis relies on the presence of either Rad5 or Rad18, which promote two distinct error-prone pathways that partially overlap with respect to lesion specificity...
- Huang J, Huen M, Kim H, Leung C, Glover J, Yu X, et al. RAD18 transmits DNA damage signalling to elicit homologous recombination repair. Nat Cell Biol. 2009;11:592-603 pubmed publisher..Here we describe a new role for the E3 ligase RAD18 as the integral component in translating the damage response signal to orchestrate homologous recombination repair ..
- Kramarz K, Mucha S, Litwin I, Barg Wojas A, Wysocki R, Dziadkowiec D. DNA Damage Tolerance Pathway Choice Through Uls1 Modulation of Srs2 SUMOylation in Saccharomyces cerevisiae. Genetics. 2017;206:513-525 pubmed publisher..Upon ULS1 deletion, accumulating Srs2-SUMO-unable to bind PCNA-takes part in an alternative PCNA-independent recombination repair salvage pathway(s). ..
- Lehner K, Jinks Robertson S. Shared genetic pathways contribute to the tolerance of endogenous and low-dose exogenous DNA damage in yeast. Genetics. 2014;198:519-30 pubmed publisher..These results have important implications when considering what constitutes a safe and acceptable level of exogenous DNA damage. ..
- Kramarz K, Litwin I, Cal Bakowska M, Szakal B, Branzei D, Wysocki R, et al. Swi2/Snf2-like protein Uls1 functions in the Sgs1-dependent pathway of maintenance of rDNA stability and alleviation of replication stress. DNA Repair (Amst). 2014;21:24-35 pubmed publisher..by deletion of ULS1 depends on a functional of Rad51 recombinase and post-replication repair pathway mediated by Rad18 and Rad5, but not on the translesion polymerase, Rev3...
- Santa Maria S, Gangavarapu V, Johnson R, Prakash L, Prakash S. Requirement of Nse1, a subunit of the Smc5-Smc6 complex, for Rad52-dependent postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:8409-18 pubmedIn Saccharomyces cerevisiae, postreplication repair (PRR) of UV-damaged DNA occurs by a Rad6-Rad18- and an Mms2-Ubc13-Rad5-dependent pathway or by a Rad52-dependent pathway...
- Davies A, Neiss A, Ulrich H. Ubiquitylation of the 9-1-1 checkpoint clamp is independent of rad6-rad18 and DNA damage. Cell. 2010;141:1080-7 pubmed publisherA recent report proposed a function of the ubiquitin conjugation factors Rad6 and Rad18 comparable to the bacterial SOS response, controlling damage-induced transcriptional activation and contributing to checkpoint signaling...
- Wood A, Krogan N, Dover J, Schneider J, Heidt J, Boateng M, et al. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol Cell. 2003;11:267-74 pubmed..These results suggest that Bre1 is the likely E3 enzyme that directs Rad6 to modify chromatin and ultimately to affect gene expression. ..
- Hishida T, Kubota Y, Carr A, Iwasaki H. RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light. Nature. 2009;457:612-5 pubmed publisher..Here we examine the response of yeast cells to CLUV and identify a key role for the RAD6-RAD18-RAD5 error-free postreplication repair (RAD6 error-free PRR) pathway in promoting cell growth and survival...
- van der Kemp P, de Padula M, Burguiere Slezak G, Ulrich H, Boiteux S. PCNA monoubiquitylation and DNA polymerase eta ubiquitin-binding domain are required to prevent 8-oxoguanine-induced mutagenesis in Saccharomyces cerevisiae. Nucleic Acids Res. 2009;37:2549-59 pubmed publisher..Here, we present evidence for cooperation between Rad18-Rad6-dependent monoubiquitylation of PCNA at K164, the damage-tolerant DNA polymerase eta and the mismatch repair ..
- Kozhina T, Korolev V. [RAD18 gene product of yeast Saccharomyces cerevisiae controls mutagenesis induced by hydrogen peroxide]. Genetika. 2012;48:551-5 pubmed..e., initiation of replication through DNA damage, is controlled by Rad6-Rad18 ubiquitin-conjugating enzyme complex...
- Daee D, Ferrari E, Longerich S, Zheng X, Xue X, Branzei D, et al. Rad5-dependent DNA repair functions of the Saccharomyces cerevisiae FANCM protein homolog Mph1. J Biol Chem. 2012;287:26563-75 pubmed publisher..pathway is epistatic with Rad5-mediated DNA damage bypass and distinct from the ICL repair pathways mediated by Rad18 and Pso2...