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Gene Review

RAD5  -  DNA helicase RAD5

Saccharomyces cerevisiae S288c

Synonyms: DNA repair protein RAD5, REV2, Radiation sensitivity protein 5, Revertibility protein 2, SNM2, ...
 
 
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Disease relevance of RAD5

 

High impact information on RAD5

  • We report that a putative tumor suppressor gene, SHPRH, is a human orthologue of yeast RAD5 [2].
  • 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 [3].
  • Genetic evidence in yeast has indicated a role for Rad5 as a ubiquitin ligase in mediating the Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen [4].
  • Inactivation of homologous recombination (HR) proteins or the helicase Srs2 reduces GCR rates elevated by the rad5 or rad18 mutation [5].
  • Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae [6].
 

Biological context of RAD5

 

Associations of RAD5 with chemical compounds

  • A leucine zipper motif preceded by a basic region is also present in RAD5 [7].
  • The cysteine-rich region may coordinate the binding of zinc; this region and the basic segment might constitute distinct DNA-binding domains in RAD5 [7].
  • Furthermore, the REV2 dependent recovery of survival could be blocked or nearly blocked by cycloheximide added at any time during repair [10].
 

Physical interactions of RAD5

  • Chain formation is catalyzed by the Mms2/Ubc13 conjugating enzyme variant/conjugating enzyme (UEV.E2) complex together with the Rad5 ubiquitin ligase [11].
 

Other interactions of RAD5

  • Further experiments revealed that a specific RAD6-RAD18-controlled subpathway, the RAD5 branch, mediates these events [12].
  • We analyze the interactions between the RAD5 and RAD18 gene products and other repair genes [8].
  • The RAD5/RAD18 pathway of mutagenic repair is dependent on the REV3-encoded translesion polymerase [8].
  • Discontinuities, which are formed in DNA strands synthesized from UV-damaged templates, are not repaired in the rad5Delta and mms2Delta mutants, thus indicating the requirement of the Rad5 protein and the Mms2-Ubc13 ubiquitin-conjugating enzyme complex in this repair process [6].
  • We suggest that newly synthesized DNA possessing discontinuities is restored to full size by a "copy choice" type of DNA synthesis which requires Rad5, a DNA-dependent ATPase, and also PCNA and Poldelta [6].

References

  1. DNA repair genes of Saccharomyces cerevisiae: complementing rad4 and rev2 mutations by plasmids which cannot be propagated in Escherichia coli. Siede, W., Eckardt-Schupp, F. Curr. Genet. (1986) [Pubmed]
  2. Human SHPRH suppresses genomic instability through proliferating cell nuclear antigen polyubiquitination. Motegi, A., Sood, R., Moinova, H., Markowitz, S.D., Liu, P.P., Myung, K. J. Cell Biol. (2006) [Pubmed]
  3. Two RING finger proteins mediate cooperation between ubiquitin-conjugating enzymes in DNA repair. Ulrich, H.D., Jentsch, S. EMBO J. (2000) [Pubmed]
  4. Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Unk, I., Hajd??, I., F??tyol, K., Szak??l, B., Blasty??k, A., Bermudez, V., Hurwitz, J., Prakash, L., Prakash, S., Haracska, L. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  5. Regulation of gross chromosomal rearrangements by ubiquitin and SUMO ligases in Saccharomyces cerevisiae. Motegi, A., Kuntz, K., Majeed, A., Smith, S., Myung, K. Mol. Cell. Biol. (2006) [Pubmed]
  6. Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Torres-Ramos, C.A., Prakash, S., Prakash, L. Mol. Cell. Biol. (2002) [Pubmed]
  7. Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome. Johnson, R.E., Henderson, S.T., Petes, T.D., Prakash, S., Bankmann, M., Prakash, L. Mol. Cell. Biol. (1992) [Pubmed]
  8. Genetic interactions between mutants of the 'error-prone' repair group of Saccharomyces cerevisiae and their effect on recombination and mutagenesis. Liefshitz, B., Steinlauf, R., Friedl, A., Eckardt-Schupp, F., Kupiec, M. Mutat. Res. (1998) [Pubmed]
  9. Deletion of the SRS2 gene suppresses elevated recombination and DNA damage sensitivity in rad5 and rad18 mutants of Saccharomyces cerevisiae. Friedl, A.A., Liefshitz, B., Steinlauf, R., Kupiec, M. Mutat. Res. (2001) [Pubmed]
  10. Analysis of mutagenic DNA repair in a thermoconditional repair mutant of Saccharomyces cerevisiae. I. Influence of cycloheximide on UV-irradiated stationary phase rev2ts cells. Siede, W., Eckardt, F., Brendel, M. Mol. Gen. Genet. (1983) [Pubmed]
  11. Ubiquitin binding site of the ubiquitin E2 variant (UEV) protein Mms2 is required for DNA damage tolerance in the yeast RAD6 pathway. Tsui, C., Raguraj, A., Pickart, C.M. J. Biol. Chem. (2005) [Pubmed]
  12. Saccharomyces cerevisiae RAD5 influences the excision repair of DNA minor groove adducts. Kiakos, K., Howard, T.T., Lee, M., Hartley, J.A., McHugh, P.J. J. Biol. Chem. (2002) [Pubmed]
 
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