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. 1997 May 15;16(10):2682–2692. doi: 10.1093/emboj/16.10.2682

rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest.

E Stewart 1, C R Chapman 1, F Al-Khodairy 1, A M Carr 1, T Enoch 1
PMCID: PMC1169879  PMID: 9184215

Abstract

In eukaryotic cells, S phase can be reversibly arrested by drugs that inhibit DNA synthesis or DNA damage. Here we show that recovery from such treatments is under genetic control and is defective in fission yeast rqh1 mutants. rqh1+, previously known as hus2+, encodes a putative DNA helicase related to the Escherichia coli RecQ helicase, with particular homology to the gene products of the human BLM and WRN genes and the Saccharomyces cerevisiae SGS1 gene. BLM and WRN are mutated in patients with Bloom's syndrome and Werner's syndrome respectively. Both syndromes are associated with genomic instability and cancer susceptibility. We show that, like BLM and SGS1, rqh1+ is required to prevent recombination and that in fission yeast suppression of inappropriate recombination is essential for reversible S phase arrest.

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Selected References

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  1. Barbet N., Muriel W. J., Carr A. M. Versatile shuttle vectors and genomic libraries for use with Schizosaccharomyces pombe. Gene. 1992 May 1;114(1):59–66. doi: 10.1016/0378-1119(92)90707-v. [DOI] [PubMed] [Google Scholar]
  2. Bartram C. R., Koske-Westphal T., Passarge E. Chromatid exchanges in ataxia telangiectasia, Bloom syndrome, Werner syndrome, and xeroderma pigmentosum. Ann Hum Genet. 1976 Jul;40(1):79–86. doi: 10.1111/j.1469-1809.1976.tb00166.x. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bootsma D., Weeda G., Vermeulen W., van Vuuren H., Troelstra C., van der Spek P., Hoeijmakers J. Nucleotide excision repair syndromes: molecular basis and clinical symptoms. Philos Trans R Soc Lond B Biol Sci. 1995 Jan 30;347(1319):75–81. doi: 10.1098/rstb.1995.0012. [DOI] [PubMed] [Google Scholar]
  5. Chevalier S., Blow J. J. Cell cycle control of replication initiation in eukaryotes. Curr Opin Cell Biol. 1996 Dec;8(6):815–821. doi: 10.1016/s0955-0674(96)80082-2. [DOI] [PubMed] [Google Scholar]
  6. Chu G., Mayne L. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases? Trends Genet. 1996 May;12(5):187–192. doi: 10.1016/0168-9525(96)10021-4. [DOI] [PubMed] [Google Scholar]
  7. Chung D. C., Rustgi A. K. DNA mismatch repair and cancer. Gastroenterology. 1995 Nov;109(5):1685–1699. doi: 10.1016/0016-5085(95)90660-6. [DOI] [PubMed] [Google Scholar]
  8. Darlington G. J., Dutkowski R., Brown W. T. Sister chromatid exchange frequencies in Progeria and Werner syndrome patients. Am J Hum Genet. 1981 Sep;33(5):762–766. [PMC free article] [PubMed] [Google Scholar]
  9. Ellis N. A., Groden J., Ye T. Z., Straughen J., Lennon D. J., Ciocci S., Proytcheva M., German J. The Bloom's syndrome gene product is homologous to RecQ helicases. Cell. 1995 Nov 17;83(4):655–666. doi: 10.1016/0092-8674(95)90105-1. [DOI] [PubMed] [Google Scholar]
  10. Enoch T., Carr A. M., Nurse P. Fission yeast genes involved in coupling mitosis to completion of DNA replication. Genes Dev. 1992 Nov;6(11):2035–2046. doi: 10.1101/gad.6.11.2035. [DOI] [PubMed] [Google Scholar]
  11. Enoch T., Gould K. L., Nurse P. Mitotic checkpoint control in fission yeast. Cold Spring Harb Symp Quant Biol. 1991;56:409–416. doi: 10.1101/sqb.1991.056.01.048. [DOI] [PubMed] [Google Scholar]
  12. Enoch T., Norbury C. Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles of p53 and ATM. Trends Biochem Sci. 1995 Oct;20(10):426–430. doi: 10.1016/s0968-0004(00)89093-3. [DOI] [PubMed] [Google Scholar]
  13. Enoch T., Nurse P. Mutation of fission yeast cell cycle control genes abolishes dependence of mitosis on DNA replication. Cell. 1990 Feb 23;60(4):665–673. doi: 10.1016/0092-8674(90)90669-6. [DOI] [PubMed] [Google Scholar]
  14. Gangloff S., McDonald J. P., Bendixen C., Arthur L., Rothstein R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol. 1994 Dec;14(12):8391–8398. doi: 10.1128/mcb.14.12.8391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gebhart E., Bauer R., Raub U., Schinzel M., Ruprecht K. W., Jonas J. B. Spontaneous and induced chromosomal instability in Werner syndrome. Hum Genet. 1988 Oct;80(2):135–139. doi: 10.1007/BF00702855. [DOI] [PubMed] [Google Scholar]
  16. German J. Bloom syndrome: a mendelian prototype of somatic mutational disease. Medicine (Baltimore) 1993 Nov;72(6):393–406. [PubMed] [Google Scholar]
  17. Gorbalenya A. E., Koonin E. V., Donchenko A. P., Blinov V. M. Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res. 1989 Jun 26;17(12):4713–4730. doi: 10.1093/nar/17.12.4713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grossenbacher-Grunder A. M., Thuriaux P. Spontaneous and UV-induced recombination in radiation-sensitive mutants of Schizosaccharomyces pombe. Mutat Res. 1981 Mar;81(1):37–48. doi: 10.1016/0027-5107(81)90085-3. [DOI] [PubMed] [Google Scholar]
  19. Hartwell L. H., Weinert T. A. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989 Nov 3;246(4930):629–634. doi: 10.1126/science.2683079. [DOI] [PubMed] [Google Scholar]
  20. Heartlein M. W., Tsuji H., Latt S. A. 5-Bromodeoxyuridine-dependent increase in sister chromatid exchange formation in Bloom's syndrome is associated with reduction in topoisomerase II activity. Exp Cell Res. 1987 Mar;169(1):245–254. doi: 10.1016/0014-4827(87)90242-4. [DOI] [PubMed] [Google Scholar]
  21. Hirano T., Funahashi S., Uemura T., Yanagida M. Isolation and characterization of Schizosaccharomyces pombe cutmutants that block nuclear division but not cytokinesis. EMBO J. 1986 Nov;5(11):2973–2979. doi: 10.1002/j.1460-2075.1986.tb04594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holm C., Goto T., Wang J. C., Botstein D. DNA topoisomerase II is required at the time of mitosis in yeast. Cell. 1985 Jun;41(2):553–563. doi: 10.1016/s0092-8674(85)80028-3. [DOI] [PubMed] [Google Scholar]
  23. Kurihara T., Inoue M., Tatsumi K. Hypersensitivity of Bloom's syndrome fibroblasts to N-ethyl-N-nitrosourea. Mutat Res. 1987 Sep;184(2):147–151. doi: 10.1016/0167-8817(87)90071-x. [DOI] [PubMed] [Google Scholar]
  24. Lehmann A. R., Carr A. M. The ataxia-telangiectasia gene: a link between checkpoint controls, neurodegeneration and cancer. Trends Genet. 1995 Oct;11(10):375–377. doi: 10.1016/s0168-9525(00)89112-x. [DOI] [PubMed] [Google Scholar]
  25. Longhese M. P., Fraschini R., Plevani P., Lucchini G. Yeast pip3/mec3 mutants fail to delay entry into S phase and to slow DNA replication in response to DNA damage, and they define a functional link between Mec3 and DNA primase. Mol Cell Biol. 1996 Jul;16(7):3235–3244. doi: 10.1128/mcb.16.7.3235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lu J., Mullen J. R., Brill S. J., Kleff S., Romeo A. M., Sternglanz R. Human homologues of yeast helicase. Nature. 1996 Oct 24;383(6602):678–679. doi: 10.1038/383678a0. [DOI] [PubMed] [Google Scholar]
  27. Moreno S., Klar A., Nurse P. Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. Methods Enzymol. 1991;194:795–823. doi: 10.1016/0076-6879(91)94059-l. [DOI] [PubMed] [Google Scholar]
  28. Murakami S., Yanagida M., Niwa O. A large circular minichromosome of Schizosaccharomyces pombe requires a high dose of type II DNA topoisomerase for its stabilization. Mol Gen Genet. 1995 Mar 20;246(6):671–679. doi: 10.1007/BF00290712. [DOI] [PubMed] [Google Scholar]
  29. Murray A. W. Creative blocks: cell-cycle checkpoints and feedback controls. Nature. 1992 Oct 15;359(6396):599–604. doi: 10.1038/359599a0. [DOI] [PubMed] [Google Scholar]
  30. Murray J. M., Doe C. L., Schenk P., Carr A. M., Lehmann A. R., Watts F. Z. Cloning and characterisation of the S. pombe rad15 gene, a homologue to the S. cerevisiae RAD3 and human ERCC2 genes. Nucleic Acids Res. 1992 Jun 11;20(11):2673–2678. doi: 10.1093/nar/20.11.2673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Paulovich A. G., Hartwell L. H. A checkpoint regulates the rate of progression through S phase in S. cerevisiae in response to DNA damage. Cell. 1995 Sep 8;82(5):841–847. doi: 10.1016/0092-8674(95)90481-6. [DOI] [PubMed] [Google Scholar]
  32. Peeper D. S., van der Eb A. J., Zantema A. The G1/S cell-cycle checkpoint in eukaryotic cells. Biochim Biophys Acta. 1994 Dec 30;1198(2-3):215–230. doi: 10.1016/0304-419x(94)90015-9. [DOI] [PubMed] [Google Scholar]
  33. Sazer S., Nurse P. A fission yeast RCC1-related protein is required for the mitosis to interphase transition. EMBO J. 1994 Feb 1;13(3):606–615. doi: 10.1002/j.1460-2075.1994.tb06298.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sazer S., Sherwood S. W. Mitochondrial growth and DNA synthesis occur in the absence of nuclear DNA replication in fission yeast. J Cell Sci. 1990 Nov;97(Pt 3):509–516. doi: 10.1242/jcs.97.3.509. [DOI] [PubMed] [Google Scholar]
  35. Sheldrick K. S., Carr A. M. Feedback controls and G2 checkpoints: fission yeast as a model system. Bioessays. 1993 Dec;15(12):775–782. doi: 10.1002/bies.950151202. [DOI] [PubMed] [Google Scholar]
  36. Uemura T., Ohkura H., Adachi Y., Morino K., Shiozaki K., Yanagida M. DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe. Cell. 1987 Sep 11;50(6):917–925. doi: 10.1016/0092-8674(87)90518-6. [DOI] [PubMed] [Google Scholar]
  37. Uemura T., Tanagida M. Mitotic spindle pulls but fails to separate chromosomes in type II DNA topoisomerase mutants: uncoordinated mitosis. EMBO J. 1986 May;5(5):1003–1010. doi: 10.1002/j.1460-2075.1986.tb04315.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Uemura T., Yanagida M. Isolation of type I and II DNA topoisomerase mutants from fission yeast: single and double mutants show different phenotypes in cell growth and chromatin organization. EMBO J. 1984 Aug;3(8):1737–1744. doi: 10.1002/j.1460-2075.1984.tb02040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Vassilev L., Russev G. Hydroxyurea treatment does not prevent initiation of DNA synthesis in Ehrlich ascites tumour cells and leads to the accumulation of short DNA fragments containing the replication origins. Biochim Biophys Acta. 1984 Feb 24;781(1-2):39–44. doi: 10.1016/0167-4781(84)90121-0. [DOI] [PubMed] [Google Scholar]
  40. Watt P. M., Hickson I. D., Borts R. H., Louis E. J. SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics. 1996 Nov;144(3):935–945. doi: 10.1093/genetics/144.3.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Watt P. M., Louis E. J., Borts R. H., Hickson I. D. Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Cell. 1995 Apr 21;81(2):253–260. doi: 10.1016/0092-8674(95)90335-6. [DOI] [PubMed] [Google Scholar]
  42. Yu C. E., Oshima J., Fu Y. H., Wijsman E. M., Hisama F., Alisch R., Matthews S., Nakura J., Miki T., Ouais S. Positional cloning of the Werner's syndrome gene. Science. 1996 Apr 12;272(5259):258–262. doi: 10.1126/science.272.5259.258. [DOI] [PubMed] [Google Scholar]
  43. al-Khodairy F., Carr A. M. DNA repair mutants defining G2 checkpoint pathways in Schizosaccharomyces pombe. EMBO J. 1992 Apr;11(4):1343–1350. doi: 10.1002/j.1460-2075.1992.tb05179.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. al-Khodairy F., Fotou E., Sheldrick K. S., Griffiths D. J., Lehmann A. R., Carr A. M. Identification and characterization of new elements involved in checkpoint and feedback controls in fission yeast. Mol Biol Cell. 1994 Feb;5(2):147–160. doi: 10.1091/mbc.5.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]

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