Genomes and Genes
Gene Symbol: RAD5
Description: DNA helicase RAD5
Alias: REV2, SNM2, DNA helicase RAD5
Species: Saccharomyces cerevisiae S288c
- Branzei D, Seki M, Enomoto T. Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in replication completion during replication stress. Genes Cells. 2004;9:1031-42 pubmed..Our results are consistent with the idea that the Rad18/Rad5/Mms2 polyubiquitination pathway is important for replication completion, perhaps by promoting a template switch ..
- 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 ..
- Gangavarapu V, Prakash S, Prakash L. Requirement of RAD52 group genes for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol. 2007;27:7758-64 pubmed..promoted by Rad6-Rad18-dependent processes that include translesion synthesis by DNA polymerases eta and zeta and a Rad5-Mms2-Ubc13-controlled postreplicational repair (PRR) pathway which repairs the discontinuities in the newly ..
- Hishida T, Hirade Y, Haruta N, Kubota Y, Iwasaki H. Srs2 plays a critical role in reversible G2 arrest upon chronic and low doses of UV irradiation via two distinct homologous recombination-dependent mechanisms in postreplication repair-deficient cells. Mol Cell Biol. 2010;30:4840-50 pubmed publisher..The first (required to suppress HR during PRR) is regulated by PCNA sumoylation, whereas the second (required for HR-dependent recovery following CLUV exposure) is regulated by CDK1-dependent phosphorylation. ..
- Chavez A, Agrawal V, Johnson F. Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. J Biol Chem. 2011;286:5119-25 pubmed publisher..These data as a whole highlight a role for Smc5/6 and Sgs1 in the resolution of Mph1-dependent HR intermediates. ..
- Minca E, Kowalski D. Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks. Mol Cell. 2010;38:649-61 pubmed publisher..b>Rad5, a PCNA polyubiquitin ligase and DNA-dependent ATPase in yeast, is orthologous to putative tumor suppressors and ..
- Saponaro M, Callahan D, Zheng X, Krejci L, Haber J, Klein H, et al. Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair. PLoS Genet. 2010;6:e1000858 pubmed publisher..We suggest that Cdk1 kinase counteracts unscheduled sumoylation of Srs2 and targets Srs2 to dismantle specific DNA structures, such as the D-loops, in a helicase-dependent manner during homologous recombinational repair. ..
- Ulrich H, Jentsch S. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. EMBO J. 2000;19:3388-97 pubmed..We show that two chromatin-associated RING finger proteins, RAD18 and RAD5, play a central role in mediating physical contacts between the members of the RAD6 pathway...
- 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..A sub-branch within the RAD6 pathway is mediated by RAD5, UBC13 and MMS2, and a comprehensive analysis of the srs2 effect on other known members of the RAD6 pathway ..
- 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...
- Halas A, Podlaska A, Derkacz J, McIntyre J, Skoneczna A, Sledziewska Gojska E. The roles of PCNA SUMOylation, Mms2-Ubc13 and Rad5 in translesion DNA synthesis in Saccharomyces cerevisiae. Mol Microbiol. 2011;80:786-97 pubmed publisherMms2, in concert with Ubc13 and Rad5, is responsible for polyubiquitination of replication processivity factor PCNA. This modification activates recombination-like DNA damage-avoidance mechanisms, which function in an error-free manner...
- 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. ..
- 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..Moreover, we show that the Rad5 protein physically associates with the single-stranded DNA regions at a processed double-strand break in vivo...
- 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. ..
- 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...
- Ulrich H. Protein-protein interactions within an E2-RING finger complex. Implications for ubiquitin-dependent DNA damage repair. J Biol Chem. 2003;278:7051-8 pubmedThe RING finger protein RAD5 interacts and cooperates with the UBC13-MMS2 ubiquitin-conjugating enzyme in postreplication DNA damage repair in yeast...
- Pages V, Bresson A, Acharya N, Prakash S, Fuchs R, Prakash L. Requirement of Rad5 for DNA polymerase zeta-dependent translesion synthesis in Saccharomyces cerevisiae. Genetics. 2008;180:73-82 pubmed publisherIn yeast, Rad6-Rad18-dependent lesion bypass involves translesion synthesis (TLS) by DNA polymerases eta or zeta or Rad5-dependent postreplication repair (PRR) in which error-free replication through the DNA lesion occurs by template ..
- 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...
- Carlile C, Pickart C, Matunis M, Cohen R. Synthesis of free and proliferating cell nuclear antigen-bound polyubiquitin chains by the RING E3 ubiquitin ligase Rad5. J Biol Chem. 2009;284:29326-34 pubmed publisher..moiety of monoubiquitinated proliferating cell nuclear antigen (monoUb-PCNA) by the E2-E3 complex of (Ubc13-Mms2)-Rad5. This promotes error-free bypass of DNA damage lesions...
- 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..of poly-ubiquitylation of the replication clamp PCNA by two cooperating E2-E3 pairs, Rad6-Rad18 and Ubc13-Mms2-Rad5. We find that the two complexes act sequentially and independently in chain initiation and stepwise elongation, ..
- Gangavarapu V, Santa Maria S, Prakash S, Prakash L. Requirement of replication checkpoint protein kinases Mec1/Rad53 for postreplication repair in yeast. MBio. 2011;2:e00079-11 pubmed publisher..pathway where lesions can be bypassed by the action of translesion synthesis (TLS) DNA polymerases ? and ? or by Rad5-mediated template switching...
- Gangavarapu V, Haracska L, Unk I, Johnson R, Prakash S, Prakash L. Mms2-Ubc13-dependent and -independent roles of Rad5 ubiquitin ligase in postreplication repair and translesion DNA synthesis in Saccharomyces cerevisiae. Mol Cell Biol. 2006;26:7783-90 pubmed..in the newly synthesized DNA opposite from DNA lesions, mediated by the Mms2-Ubc13 ubiquitin-conjugating enzyme and Rad5. Rad5 is an SWI/SNF family ATPase, and additionally, it functions as a ubiquitin ligase in the ubiquitin ..
- Blastyak A, Pintér L, Unk I, Prakash L, Prakash S, Haracska L. Yeast Rad5 protein required for postreplication repair has a DNA helicase activity specific for replication fork regression. Mol Cell. 2007;28:167-75 pubmed..through DNA lesions is mediated by different Rad6-Rad18-dependent means, which include translesion synthesis and a Rad5-dependent postreplicational repair pathway that repairs the discontinuities that form in the DNA synthesized from ..
- 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..RAD6 group genes can be exclusively divided into three rather than two independent subpathways represented by the RAD5, POL30, and REV3 genes; the REV3 pathway is largely mutagenic, whereas the RAD5 and the POL30 pathways are deemed ..
- Ortiz BazÃ¡n M, Gallo FernÃ¡ndez M, Saugar I, JimÃ©nez MartÃn A, VÃ¡zquez M, Tercero J. Rad5 plays a major role in the cellular response to DNA damage during chromosome replication. Cell Rep. 2014;9:460-8 pubmed publisher..Here, we show that Rad5(HLTF/SHPRH), which mediates the error-free branch, has a major role in the response to DNA damage caused by methyl ..
- 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...
- Fan H, Cheng K, Klein H. Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae. Genetics. 1996;142:749-59 pubmed..Because mutations in SOH1, RPB2 and SUA7 suppress the hyperrecombination phenotype of hpr1 mutants, this suggests a link between recombination in direct repeats and transcription. ..
- 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 pubmed..In 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...
- Fallet E, Jolivet P, Soudet J, Lisby M, Gilson E, Teixeira M. Length-dependent processing of telomeres in the absence of telomerase. Nucleic Acids Res. 2014;42:3648-65 pubmed publisher..We then asked whether replication repair pathways contribute to this mechanism. We uncovered that Rad5, a DNA helicase/Ubiquitin ligase of the error-free branch of the DNA damage tolerance (DDT) pathway, associates ..
- 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. ..
- Schmidt K, Kolodner R. Requirement of Rrm3 helicase for repair of spontaneous DNA lesions in cells lacking Srs2 or Sgs1 helicase. Mol Cell Biol. 2004;24:3213-26 pubmed..These observations identify Rrm3 as a new member of a network of pathways, involving Sgs1 and Srs2 helicases and Mus81 endonuclease, suggested to act during repair of stalled replication forks. ..
- Xu X, Lin A, Zhou C, Blackwell S, Zhang Y, Wang Z, et al. Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1. Nucleic Acids Res. 2016;44:5231-45 pubmed publisher..b>Rad5 has been placed in the error-free branch of DDT because it contains an E3 ligase domain required for PCNA ..
- Daraba A, Gali V, Halmai M, Haracska L, Unk I. Def1 promotes the degradation of Pol3 for polymerase exchange to occur during DNA-damage--induced mutagenesis in Saccharomyces cerevisiae. PLoS Biol. 2014;12:e1001771 pubmed publisher..Our results imply that TLS polymerases carry out DNA lesion bypass only after the Def1-assisted removal of Pol3 from the stalled replication fork...
- Kim E, Siede W. The available SRL3 deletion strain of Saccharomyces cerevisiae contains a truncation of DNA damage tolerance protein Mms2: Implications for Srl3 and Mms2 functions. Internet J Microbiol. 2009;8:8 pubmed..Srl3, on the other hand, does not appear to influence DNA damage sensitivity or spontaneous mutability if deleted. However, the absence of these phenotypes does not contradict its likely role as a positive regulator of dNTP levels. ..
- Game J, Kaufman P. Role of Saccharomyces cerevisiae chromatin assembly factor-I in repair of ultraviolet radiation damage in vivo. Genetics. 1999;151:485-97 pubmed..We find an increased loss of telomeric gene silencing in rad6Delta cac1Delta and rad18Delta cac1Delta double mutants, suggesting that CAF-I and multiple factors in the postreplicative repair pathway influence chromosome structure. ..
- 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..Deletion of RAD5 or MMS2 had an effect on pol31 ts/cs mutants similar to that of RAD18, whereas deletion of RAD30 or REV3 had no ..
- Pessoa Brandao L, Sclafani R. CDC7/DBF4 functions in the translesion synthesis branch of the RAD6 epistasis group in Saccharomyces cerevisiae. Genetics. 2004;167:1597-610 pubmed..Several genes have been determined to function in separate branches within this group, including RAD5, REV3/REV7 (Pol zeta), RAD30 (Pol eta), and POL30 (PCNA)...
- Ribar B, Prakash L, Prakash S. Requirement of ELC1 for RNA polymerase II polyubiquitylation and degradation in response to DNA damage in Saccharomyces cerevisiae. Mol Cell Biol. 2006;26:3999-4005 pubmed
- Siler J, Xia B, Wong C, Kath M, Bi X. Cell cycle-dependent positive and negative functions of Fun30 chromatin remodeler in DNA damage response. DNA Repair (Amst). 2017;50:61-70 pubmed publisher..we have recently found Fun30 to also play a negative role in cellular tolerance to MMS and HU in the absence of the Rad5-dependent DNA damage tolerance pathway...
- Hishida T, Ohya T, Kubota Y, Kamada Y, Shinagawa H. Functional and physical interaction of yeast Mgs1 with PCNA: impact on RAD6-dependent DNA damage tolerance. Mol Cell Biol. 2006;26:5509-17 pubmed..The proposed roles for Mgs1, Srs2, and modified PCNA during replication arrest highlight the importance of modulating the RAD6 and RAD52 pathways to avoid genome instability. ..
- 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 publisher..Instead, our findings suggest that ubiquitylation of the 9-1-1 complex may be a background reaction that in some cases can mediate proteasomal degradation. ..
- Jain D, Siede W. Rad5 template switch pathway of DNA damage tolerance determines synergism between cisplatin and NSC109268 in Saccharomyces cerevisiae. PLoS ONE. 2013;8:e77666 pubmed publisher..A survey of various yeast deletion mutants converged on the Rad5 pathway of DNA damage tolerance by template switching as the likely target pathway of NSC109268 in mediating ..
- Godin S, Zhang Z, Herken B, Westmoreland J, Lee A, Mihalevic M, et al. The Shu complex promotes error-free tolerance of alkylation-induced base excision repair products. Nucleic Acids Res. 2016;44:8199-215 pubmed publisher..Together, our work demonstrates that the Shu complex's promotion of Rad51 pre-synaptic filaments is critical for high-fidelity bypass of multiple replication-blocking lesion. ..
- Xue X, Choi K, Bonner J, Chiba T, Kwon Y, Xu Y, et al. Restriction of replication fork regression activities by a conserved SMC complex. Mol Cell. 2014;56:436-45 pubmed publisher..Our findings provide molecular insights into replication fork repair regulation and uncover a role of Smc5-Smc6 in directing Mph1 activity toward a specific biochemical outcome. ..
- Ye Y, Kirkham McCarthy L, Lahue R. The Saccharomyces cerevisiae Mre11-Rad50-Xrs2 complex promotes trinucleotide repeat expansions independently of homologous recombination. DNA Repair (Amst). 2016;43:1-8 pubmed publisher..Epistasis between MRX and post-replication repair (PRR) was tested. PRR protects against expansions, so a rad5 mutant gave a high expansion rate...
- Choi D, Min M, Kim M, Lee R, Kwon S, Bae S. Hrq1 facilitates nucleotide excision repair of DNA damage induced by 4-nitroquinoline-1-oxide and cisplatin in Saccharomyces cerevisiae. J Microbiol. 2014;52:292-8 pubmed publisher..Overexpression of Hrq1K318A helicase-deficient protein rendered mutant cells more sensitive to 4-NQO and cisplatin, suggesting that helicase activity is required for the proper function of Hrq1 in NER. ..
- Mániková D, Vlasáková D, Letavayová L, Klobucnikova V, Griac P, Chovanec M. Selenium toxicity toward yeast as assessed by microarray analysis and deletion mutant library screen: a role for DNA repair. Chem Res Toxicol. 2012;25:1598-608 pubmed publisher..In addition, we suggest that SeL toxicity also originates from damage to cellular proteins, including those acting in DNA damage response and repair...
- 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..This pathway is epistatic with Rad5-mediated DNA damage bypass and distinct from the ICL repair pathways mediated by Rad18 and Pso2...
- Choi K, Batke S, Szakal B, Lowther J, Hao F, Sarangi P, et al. Concerted and differential actions of two enzymatic domains underlie Rad5 contributions to DNA damage tolerance. Nucleic Acids Res. 2015;43:2666-77 pubmed publisher..Here we examined the conserved budding yeast Rad5 protein that has both ubiquitin ligase and DNA helicase activities...
- Demogines A, Smith E, Kruglyak L, Alani E. Identification and dissection of a complex DNA repair sensitivity phenotype in Baker's yeast. PLoS Genet. 2008;4:e1000123 pubmed publisher..We mapped a major quantitative trait locus (QTL), RAD5, and identified the exact polymorphism within this locus responsible for 4-NQO sensitivity...
- O Neill B, Hanway D, Winzeler E, Romesberg F. Coordinated functions of WSS1, PSY2 and TOF1 in the DNA damage response. Nucleic Acids Res. 2004;32:6519-30 pubmed..Tof1 is known to be involved in stabilizing stalled replication forks and our data suggest that Wss1 and Psy2 similarly function to stabilize or process stalled or collapsed replication forks. ..
- Shemesh K, Sebesta M, Pacesa M, Sau S, Bronstein A, Parnas O, et al. A structure-function analysis of the yeast Elg1 protein reveals the importance of PCNA unloading in genome stability maintenance. Nucleic Acids Res. 2017;45:3189-3203 pubmed publisher..Additionally, we find that mutations in ELG1 suppress the sensitivity of rad5? mutants to DNA damage by allowing trans-lesion synthesis to take place...
- 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. ..
- Bi X, Yu Q, Siler J, Li C, Khan A. Functions of Fun30 chromatin remodeler in regulating cellular resistance to genotoxic stress. PLoS ONE. 2015;10:e0121341 pubmed publisher..On the other hand, we show that Fun30 deletion suppresses the MMS- and HU-sensitivity of cells lacking the Rad5/Mms2/Ubc13-dependent error-free DNA damage tolerance mechanism...
- Allen Soltero S, Martinez S, Putnam C, Kolodner R. A saccharomyces cerevisiae RNase H2 interaction network functions to suppress genome instability. Mol Cell Biol. 2014;34:1521-34 pubmed publisher..This analysis suggests that cells with RNase H2 defects have increased levels of DNA damage and depend on other pathways of DNA metabolism to overcome the deleterious effects of this DNA damage. ..
- 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). ..
- Hammet A, Pike B, Heierhorst J. Posttranscriptional regulation of the RAD5 DNA repair gene by the Dun1 kinase and the Pan2-Pan3 poly(A)-nuclease complex contributes to survival of replication blocks. J Biol Chem. 2002;277:22469-74 pubmed..Interestingly, the RAD5 gene involved in error-free postreplication repair pathways was specifically up-regulated in dun1pan2 double ..
- Becker J, Nguyen H, Wang X, Bielinsky A. Mcm10 deficiency causes defective-replisome-induced mutagenesis and a dependency on error-free postreplicative repair. Cell Cycle. 2014;13:1737-48 pubmed publisher..Thus, it appears that DRIM is not proficient to fill replication gaps in pol1-1 and mcm10-1 mutants. Moreover, the ability to correctly prime nascent DNA may be a crucial prerequisite to initiate error-free PRR. ..
- Herzberg K, Bashkirov V, Rolfsmeier M, Haghnazari E, McDonald W, Anderson S, et al. Phosphorylation of Rad55 on serines 2, 8, and 14 is required for efficient homologous recombination in the recovery of stalled replication forks. Mol Cell Biol. 2006;26:8396-409 pubmed..These results suggest that Rad55-S2,8,14 phosphorylation activates recombinational repair, allowing for faster recovery after genotoxic stress. ..
- 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. ..