Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2003 Jun;164(2):457–467. doi: 10.1093/genetics/164.2.457

Repair of damaged and mismatched DNA by the XPC homologues Rhp41 and Rhp42 of fission yeast.

Thomas M Marti 1, Christophe Kunz 1, Oliver Fleck 1
PMCID: PMC1462589  PMID: 12807767

Abstract

Rhp41 and Rhp42 of Schizosaccharomyces pombe are homologues of human XPC, which is involved in nucleotide excision repair (NER) of damaged DNA. Inactivation of rhp41 caused moderate sensitivity to ultraviolet (UV) radiation. In addition, an increase of mitotic mutation rates was observed in the rhp41 mutant, which was dependent on active translesion polymerase Z. UV sensitivity and mutation rates were not different between rhp42 and wild type, but compared to rhp41 were further increased in rhp41 rhp42 cells. Transcription of the fbp1 gene (induced in vegetative cells) and of the SPBC1289.14 gene (induced during meiosis) was strongly blocked by UV-induced damages in the rhp41 mutant, but not, or only slightly, reduced in rhp42 background. NER-dependent short-patch repair of mismatches formed during meiosis was slightly affected in rhp41, moderately affected in rhp42, and absent in rhp41 rhp42. Epistasis analysis with rhp7 and rhp26 indicates that Rhp41 and Rhp42 are both involved in the global genome and transcription-coupled repair subpathways of NER. Rhp41 plays a major role in damage repair and Rhp42 in mismatch repair.

Full Text

The Full Text of this article is available as a PDF (234.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bateman Alex, Birney Ewan, Cerruti Lorenzo, Durbin Richard, Etwiller Laurence, Eddy Sean R., Griffiths-Jones Sam, Howe Kevin L., Marshall Mhairi, Sonnhammer Erik L. L. The Pfam protein families database. Nucleic Acids Res. 2002 Jan 1;30(1):276–280. doi: 10.1093/nar/30.1.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bentley N. J., Holtzman D. A., Flaggs G., Keegan K. S., DeMaggio A., Ford J. C., Hoekstra M., Carr A. M. The Schizosaccharomyces pombe rad3 checkpoint gene. EMBO J. 1996 Dec 2;15(23):6641–6651. [PMC free article] [PubMed] [Google Scholar]
  3. Bhui-Kaur A., Goodman M. F., Tower J. DNA mismatch repair catalyzed by extracts of mitotic, postmitotic, and senescent Drosophila tissues and involvement of mei-9 gene function for full activity. Mol Cell Biol. 1998 Mar;18(3):1436–1443. doi: 10.1128/mcb.18.3.1436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Broomfield S., Hryciw T., Xiao W. DNA postreplication repair and mutagenesis in Saccharomyces cerevisiae. Mutat Res. 2001 Aug 9;486(3):167–184. doi: 10.1016/s0921-8777(01)00091-x. [DOI] [PubMed] [Google Scholar]
  5. Burgers P. M., Koonin E. V., Bruford E., Blanco L., Burtis K. C., Christman M. F., Copeland W. C., Friedberg E. C., Hanaoka F., Hinkle D. C. Eukaryotic DNA polymerases: proposal for a revised nomenclature. J Biol Chem. 2001 Sep 28;276(47):43487–43490. doi: 10.1074/jbc.R100056200. [DOI] [PubMed] [Google Scholar]
  6. Bähler J., Wu J. Q., Longtine M. S., Shah N. G., McKenzie A., 3rd, Steever A. B., Wach A., Philippsen P., Pringle J. R. Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast. 1998 Jul;14(10):943–951. doi: 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  7. Bähler J., Wyler T., Loidl J., Kohli J. Unusual nuclear structures in meiotic prophase of fission yeast: a cytological analysis. J Cell Biol. 1993 Apr;121(2):241–256. doi: 10.1083/jcb.121.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CURR J. F., VINE R. S. Carcinoma of the adrenal cortex causing feminism in an adult male. J R Army Med Corps. 1953 Jul;99(4):146–158. [PubMed] [Google Scholar]
  9. Carpenter A. T. Mismatch repair, gene conversion, and crossing-over in two recombination-defective mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5961–5965. doi: 10.1073/pnas.79.19.5961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Caspari T., Carr A. M. DNA structure checkpoint pathways in Schizosaccharomyces pombe. Biochimie. 1999 Jan-Feb;81(1-2):173–181. doi: 10.1016/s0300-9084(99)80050-9. [DOI] [PubMed] [Google Scholar]
  11. Fleck O., Lehmann E., Schär P., Kohli J. Involvement of nucleotide-excision repair in msh2 pms1-independent mismatch repair. Nat Genet. 1999 Mar;21(3):314–317. doi: 10.1038/6838. [DOI] [PubMed] [Google Scholar]
  12. Friedberg E. C., Gerlach V. L. Novel DNA polymerases offer clues to the molecular basis of mutagenesis. Cell. 1999 Aug 20;98(4):413–416. doi: 10.1016/s0092-8674(00)81970-4. [DOI] [PubMed] [Google Scholar]
  13. Friedberg E. C. How nucleotide excision repair protects against cancer. Nat Rev Cancer. 2001 Oct;1(1):22–33. doi: 10.1038/35094000. [DOI] [PubMed] [Google Scholar]
  14. Fukumoto Yasunori, Hiyama Hideki, Yokoi Masayuki, Nakaseko Yukinobu, Yanagida Mitsuhiro, Hanaoka Fumio. Two budding yeast RAD4 homologs in fission yeast play different roles in the repair of UV-induced DNA damage. DNA Repair (Amst) 2002 Oct 1;1(10):833–845. doi: 10.1016/s1568-7864(02)00108-8. [DOI] [PubMed] [Google Scholar]
  15. Goldstein A. L., McCusker J. H. Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae. Yeast. 1999 Oct;15(14):1541–1553. doi: 10.1002/(SICI)1097-0061(199910)15:14<1541::AID-YEA476>3.0.CO;2-K. [DOI] [PubMed] [Google Scholar]
  16. Grimm C., Schaer P., Munz P., Kohli J. The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe. Mol Cell Biol. 1991 Jan;11(1):289–298. doi: 10.1128/mcb.11.1.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoeijmakers J. H. Genome maintenance mechanisms for preventing cancer. Nature. 2001 May 17;411(6835):366–374. doi: 10.1038/35077232. [DOI] [PubMed] [Google Scholar]
  18. Hohl M., Christensen O., Kunz C., Naegeli H., Fleck O. Binding and repair of mismatched DNA mediated by Rhp14, the fission yeast homologue of human XPA. J Biol Chem. 2001 Jun 14;276(33):30766–30772. doi: 10.1074/jbc.M104039200. [DOI] [PubMed] [Google Scholar]
  19. Huang J. C., Svoboda D. L., Reardon J. T., Sancar A. Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5' and the 6th phosphodiester bond 3' to the photodimer. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3664–3668. doi: 10.1073/pnas.89.8.3664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kunz C., Fleck O. Role of the DNA repair nucleases Rad13, Rad2 and Uve1 of Schizosaccharomyces pombe in mismatch correction. J Mol Biol. 2001 Oct 19;313(2):241–253. doi: 10.1006/jmbi.2001.5054. [DOI] [PubMed] [Google Scholar]
  21. Lombaerts M., Goeloe J. I., den Dulk H., Brandsma J. A., Brouwer J. Identification and characterization of the rhp23(+) DNA repair gene in Schizosaccharomyces pombe. Biochem Biophys Res Commun. 2000 Feb 5;268(1):210–215. doi: 10.1006/bbrc.2000.2100. [DOI] [PubMed] [Google Scholar]
  22. Lombaerts M., Peltola P. H., Visse R., den Dulk H., Brandsma J. A., Brouwer J. Characterization of the rhp7(+) and rhp16(+) genes in Schizosaccharomyces pombe. Nucleic Acids Res. 1999 Sep 1;27(17):3410–3416. doi: 10.1093/nar/27.17.3410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Masuda Yuji, Takahashi Mamoru, Fukuda Saburo, Sumii Masaharu, Kamiya Kenji. Mechanisms of dCMP transferase reactions catalyzed by mouse Rev1 protein. J Biol Chem. 2001 Nov 15;277(4):3040–3046. doi: 10.1074/jbc.M110149200. [DOI] [PubMed] [Google Scholar]
  24. Masutani C., Kusumoto R., Yamada A., Dohmae N., Yokoi M., Yuasa M., Araki M., Iwai S., Takio K., Hanaoka F. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature. 1999 Jun 17;399(6737):700–704. doi: 10.1038/21447. [DOI] [PubMed] [Google Scholar]
  25. Mata Juan, Lyne Rachel, Burns Gavin, Bähler Jürg. The transcriptional program of meiosis and sporulation in fission yeast. Nat Genet. 2002 Aug 5;32(1):143–147. doi: 10.1038/ng951. [DOI] [PubMed] [Google Scholar]
  26. McCready S. J., Osman1 F., Yasui A. Repair of UV damage in the fission yeast Schizosaccharomyces pombe. Mutat Res. 2000 Jun 30;451(1-2):197–210. doi: 10.1016/s0027-5107(00)00050-6. [DOI] [PubMed] [Google Scholar]
  27. McHugh P. J., Gill R. D., Waters R., Hartley J. A. Excision repair of nitrogen mustard-DNA adducts in Saccharomyces cerevisiae. Nucleic Acids Res. 1999 Aug 15;27(16):3259–3266. doi: 10.1093/nar/27.16.3259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Missura M., Buterin T., Hindges R., Hübscher U., Kaspárková J., Brabec V., Naegeli H. Double-check probing of DNA bending and unwinding by XPA-RPA: an architectural function in DNA repair. EMBO J. 2001 Jul 2;20(13):3554–3564. doi: 10.1093/emboj/20.13.3554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nelson J. R., Lawrence C. W., Hinkle D. C. Deoxycytidyl transferase activity of yeast REV1 protein. Nature. 1996 Aug 22;382(6593):729–731. doi: 10.1038/382729a0. [DOI] [PubMed] [Google Scholar]
  30. Prakash S., Prakash L. Nucleotide excision repair in yeast. Mutat Res. 2000 Jun 30;451(1-2):13–24. doi: 10.1016/s0027-5107(00)00037-3. [DOI] [PubMed] [Google Scholar]
  31. Reagan M. S., Friedberg E. C. Recovery of RNA polymerase II synthesis following DNA damage in mutants of Saccharomyces cerevisiae defective in nucleotide excision repair. Nucleic Acids Res. 1997 Nov 1;25(21):4257–4263. doi: 10.1093/nar/25.21.4257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roche H., Gietz R. D., Kunz B. A. Specificity of the yeast rev3 delta antimutator and REV3 dependency of the mutator resulting from a defect (rad1 delta) in nucleotide excision repair. Genetics. 1994 Jul;137(3):637–646. doi: 10.1093/genetics/137.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rudolph C., Fleck O., Kohli J. Schizosaccharomyces pombe exo1 is involved in the same mismatch repair pathway as msh2 and pms1. Curr Genet. 1998 Dec;34(5):343–350. doi: 10.1007/s002940050405. [DOI] [PubMed] [Google Scholar]
  34. Rudolph C., Kunz C., Parisi S., Lehmann E., Hartsuiker E., Fartmann B., Kramer W., Kohli J., Fleck O. The msh2 gene of Schizosaccharomyces pombe is involved in mismatch repair, mating-type switching, and meiotic chromosome organization. Mol Cell Biol. 1999 Jan;19(1):241–250. doi: 10.1128/mcb.19.1.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Schweingruber A. M., Fankhauser H., Dlugonski J., Steinmann-Loss C., Schweingruber M. E. Isolation and characterization of regulatory mutants from Schizosaccharomyces pombe involved in thiamine-regulated gene expression. Genetics. 1992 Mar;130(3):445–449. doi: 10.1093/genetics/130.3.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Schär P., Kohli J. Marker effects of G to C transversions on intragenic recombination and mismatch repair in Schizosaccharomyces pombe. Genetics. 1993 Apr;133(4):825–835. doi: 10.1093/genetics/133.4.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sugasawa K., Ng J. M., Masutani C., Iwai S., van der Spek P. J., Eker A. P., Hanaoka F., Bootsma D., Hoeijmakers J. H. Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell. 1998 Aug;2(2):223–232. doi: 10.1016/s1097-2765(00)80132-x. [DOI] [PubMed] [Google Scholar]
  38. Thoma F. Light and dark in chromatin repair: repair of UV-induced DNA lesions by photolyase and nucleotide excision repair. EMBO J. 1999 Dec 1;18(23):6585–6598. doi: 10.1093/emboj/18.23.6585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tornier C., Bessone S., Varlet I., Rudolph C., Darmon M., Fleck O. Requirement for Msh6, but not for Swi4 (Msh3), in Msh2-dependent repair of base-base mismatches and mononucleotide loops in Schizosaccharomyces pombe. Genetics. 2001 May;158(1):65–75. doi: 10.1093/genetics/158.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Verhage R. A., van Gool A. J., de Groot N., Hoeijmakers J. H., van de Putte P., Brouwer J. Double mutants of Saccharomyces cerevisiae with alterations in global genome and transcription-coupled repair. Mol Cell Biol. 1996 Feb;16(2):496–502. doi: 10.1128/mcb.16.2.496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Verhage R., Zeeman A. M., de Groot N., Gleig F., Bang D. D., van de Putte P., Brouwer J. The RAD7 and RAD16 genes, which are essential for pyrimidine dimer removal from the silent mating type loci, are also required for repair of the nontranscribed strand of an active gene in Saccharomyces cerevisiae. Mol Cell Biol. 1994 Sep;14(9):6135–6142. doi: 10.1128/mcb.14.9.6135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Volker M., Moné M. J., Karmakar P., van Hoffen A., Schul W., Vermeulen W., Hoeijmakers J. H., van Driel R., van Zeeland A. A., Mullenders L. H. Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell. 2001 Jul;8(1):213–224. doi: 10.1016/s1097-2765(01)00281-7. [DOI] [PubMed] [Google Scholar]
  43. Watanabe Y., Lino Y., Furuhata K., Shimoda C., Yamamoto M. The S.pombe mei2 gene encoding a crucial molecule for commitment to meiosis is under the regulation of cAMP. EMBO J. 1988 Mar;7(3):761–767. doi: 10.1002/j.1460-2075.1988.tb02873.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wood V., Gwilliam R., Rajandream M-A, Lyne M., Lyne R., Stewart A., Sgouros J., Peat N., Hayles J., Baker S. The genome sequence of Schizosaccharomyces pombe. Nature. 2002 Feb 21;415(6874):871–880. doi: 10.1038/nature724. [DOI] [PubMed] [Google Scholar]
  45. Xiao W., Chow B. L. Synergism between yeast nucleotide and base excision repair pathways in the protection against DNA methylation damage. Curr Genet. 1998 Feb;33(2):92–99. doi: 10.1007/s002940050313. [DOI] [PubMed] [Google Scholar]
  46. Yokoi M., Masutani C., Maekawa T., Sugasawa K., Ohkuma Y., Hanaoka F. The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA. J Biol Chem. 2000 Mar 31;275(13):9870–9875. doi: 10.1074/jbc.275.13.9870. [DOI] [PubMed] [Google Scholar]
  47. Yonemasu R., McCready S. J., Murray J. M., Osman F., Takao M., Yamamoto K., Lehmann A. R., Yasui A. Characterization of the alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe. Nucleic Acids Res. 1997 Apr 15;25(8):1553–1558. doi: 10.1093/nar/25.8.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Zhang Yanbin, Wu Xiaohua, Rechkoblit Olga, Geacintov Nicholas E., Taylor John-Stephen, Wang Zhigang. Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion. Nucleic Acids Res. 2002 Apr 1;30(7):1630–1638. doi: 10.1093/nar/30.7.1630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. de Boer J., Hoeijmakers J. H. Nucleotide excision repair and human syndromes. Carcinogenesis. 2000 Mar;21(3):453–460. doi: 10.1093/carcin/21.3.453. [DOI] [PubMed] [Google Scholar]
  50. de Laat W. L., Jaspers N. G., Hoeijmakers J. H. Molecular mechanism of nucleotide excision repair. Genes Dev. 1999 Apr 1;13(7):768–785. doi: 10.1101/gad.13.7.768. [DOI] [PubMed] [Google Scholar]
  51. van Gool A. J., Verhage R., Swagemakers S. M., van de Putte P., Brouwer J., Troelstra C., Bootsma D., Hoeijmakers J. H. RAD26, the functional S. cerevisiae homolog of the Cockayne syndrome B gene ERCC6. EMBO J. 1994 Nov 15;13(22):5361–5369. doi: 10.1002/j.1460-2075.1994.tb06871.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES