Home LiteratureArticle Details
PMID: 11641278 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease.

Genes & development ·Vol. 15 ·No. 20 ·2001-10-15 ·Pages 2730-40

Kaliraman V, Mullen JR, Fricke WM, Bastin-Shanower SA, Brill SJ

Abstract

The RecQ DNA helicases, human BLM and yeast Sgs1, form a complex with topoisomerase III (Top3) and are thought to act during DNA replication to restart forks that have paused due to DNA damage or topological stress. We have shown previously that yeast cells lacking SGS1 or TOP3 require MMS4 and MUS81 for viability. Here we show that Mms4 and Mus81 form a heterodimeric structure-specific endonuclease that cleaves branched DNA. Both subunits are required for optimal expression, substrate binding, and nuclease activity. Mms4 and Mus81 are conserved proteins related to the Rad1-Rad10 (XPF/ERCC1) endonuclease required for nucleotide excision repair (NER). However, the Mms4-Mus81 endonuclease is 25 times more active on branched duplex DNA and replication fork substrates than simple Y-forms, the preferred substrate for the NER complexes. We also present genetic data that indicate a novel role for Mms4-Mus81 in meiotic recombination. Our results suggest that stalled replication forks are substrates for Mms4-Mus81 cleavage-particularly in the absence of Sgs1 or BLM. Repair of this double-strand break (DSB) by homologous recombination may be responsible for the elevated levels of sister chromatid exchange (SCE) found in BLM(-/-) cells.

MeSH Terms
DNA Helicases/genetics,metabolism DNA Primers/chemistry DNA Repair DNA Replication/genetics DNA Topoisomerases, Type I/genetics,metabolism DNA-Binding Proteins/genetics,metabolism Endonucleases/metabolism Flap Endonucleases Fungal Proteins/chemistry,genetics,metabolism Genetic Complementation Test Meiosis Mutation Plasmids Precipitin Tests Protein Binding RecQ Helicases Recombinant Proteins/isolation & purification Recombination, Genetic Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins Spores, Fungal/physiology Trans-Activators/genetics,metabolism
Chemicals
DNA Primers DNA-Binding Proteins Fungal Proteins Recombinant Proteins Saccharomyces cerevisiae Proteins Trans-Activators Endonucleases Flap Endonucleases MUS81 protein, S cerevisiae MMS4 protein, S cerevisiae SGS1 protein, S cerevisiae DNA Helicases RecQ Helicases DNA Topoisomerases, Type I
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kaliraman V
Department of Molecular Biology and Biochemistry Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA.
Mullen J R
Fricke W M
Bastin-Shanower S A
Brill S J
References (50)
50 references, click to expand
  1. The role of DNA topoisomerases in recombination and genome stability: a double-edged sword?
    Cell. 1990 Aug 10;62(3):403-6 PMID: 2165864
  2. Identification of a potent decatenating enzyme from Escherichia coli.
    J Biol Chem. 1988 Sep 15;263(26):13366-73 PMID: 2843517
  3. DNA topoisomerases: why so many?
    J Biol Chem. 1991 Apr 15;266(11):6659-62 PMID: 1849888
  4. Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase.
    J Biol Chem. 1992 Aug 25;267(24):17178-85 PMID: 1324925
  5. Replication-dependent sister chromatid recombination in rad1 mutants of Saccharomyces cerevisiae.
    Genetics. 1993 Mar;133(3):469-87 PMID: 8454200
  6. Yeast DNA recombination and repair proteins Rad1 and Rad10 constitute a complex in vivo mediated by localized hydrophobic domains.
    Mol Microbiol. 1993 Jun;8(6):1177-88 PMID: 8361362
  7. Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins.
    Proc Natl Acad Sci U S A. 1994 May 24;91(11):5017-21 PMID: 8197175
  8. Specific cleavage of model recombination and repair intermediates by the yeast Rad1-Rad10 DNA endonuclease.
    Science. 1994 Sep 30;265(5181):2082-5 PMID: 8091230
  9. Holliday junction cleavage by yeast Rad1 protein.
    Nature. 1994 Oct 6;371(6497):531-4 PMID: 7935767
  10. 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):8391-8 PMID: 7969174
  11. The structure-selectivity and sequence-preference of the junction-resolving enzyme CCE1 of Saccharomyces cerevisiae.
    J Mol Biol. 1996 Mar 29;257(2):330-41 PMID: 8609627
  12. A new efficient gene disruption cassette for repeated use in budding yeast.
    Nucleic Acids Res. 1996 Jul 1;24(13):2519-24 PMID: 8692690
  13. Identification of functional domains within the RAD1.RAD10 repair and recombination endonuclease of Saccharomyces cerevisiae.
    J Biol Chem. 1996 Aug 23;271(34):20551-8 PMID: 8702799
  14. 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):935-45 PMID: 8913739
  15. recF and recR are required for the resumption of replication at DNA replication forks in Escherichia coli.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3714-9 PMID: 9108043
  16. rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest.
    EMBO J. 1997 May 15;16(10):2682-92 PMID: 9184215
  17. The RPA32 subunit of human replication protein A contains a single-stranded DNA-binding domain.
    J Biol Chem. 1998 Feb 13;273(7):3932-6 PMID: 9461578
  18. DNA structural elements required for ERCC1-XPF endonuclease activity.
    J Biol Chem. 1998 Apr 3;273(14):7835-42 PMID: 9525876
  19. Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins.
    Nature. 1998 May 7;393(6680):91-4 PMID: 9590697
  20. Mms4, a putative transcriptional (co)activator, protects Saccharomyces cerevisiae cells from endogenous and environmental DNA damage.
    Mol Gen Genet. 1998 Apr;257(6):614-23 PMID: 9604884
  21. Mapping of interaction domains between human repair proteins ERCC1 and XPF.
    Nucleic Acids Res. 1998 Sep 15;26(18):4146-52 PMID: 9722633
  22. The premature ageing syndrome protein, WRN, is a 3'-->5' exonuclease.
    Nat Genet. 1998 Oct;20(2):114-6 PMID: 9771700
  23. RuvAB acts at arrested replication forks.
    Cell. 1998 Oct 30;95(3):419-30 PMID: 9814711
  24. Conserved domains in DNA repair proteins and evolution of repair systems.
    Nucleic Acids Res. 1999 Mar 1;27(5):1223-42 PMID: 9973609
  25. The essential role of yeast topoisomerase III in meiosis depends on recombination.
    EMBO J. 1999 Mar 15;18(6):1701-11 PMID: 10075939
  26. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  27. RecQ helicase and topoisomerase III comprise a novel DNA strand passage function: a conserved mechanism for control of DNA recombination.
    Mol Cell. 1999 May;3(5):611-20 PMID: 10360177
  28. Binding specificity determines polarity of DNA unwinding by the Sgs1 protein of S. cerevisiae.
    J Mol Biol. 1999 Jun 4;289(2):235-48 PMID: 10366502
  29. Defending genome integrity during DNA replication: a proposed role for RecQ family helicases.
    Bioessays. 1999 Apr;21(4):286-94 PMID: 10377891
  30. Topoisomerase III is essential for accurate nuclear division in Schizosaccharomyces pombe.
    Nucleic Acids Res. 1999 Oct 15;27(20):4050-8 PMID: 10497270
  31. Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae.
    Yeast. 1999 Oct;15(14):1541-53 PMID: 10514571
  32. RecQ and RecJ process blocked replication forks prior to the resumption of replication in UV-irradiated Escherichia coli.
    Mol Gen Genet. 1999 Oct;262(3):543-51 PMID: 10589843
  33. The Werner syndrome gene product co-purifies with the DNA replication complex and interacts with PCNA and topoisomerase I.
    J Biol Chem. 1999 Dec 31;274(53):37795-9 PMID: 10608841
  34. Bloom's syndrome gene suppresses premature ageing caused by Sgs1 deficiency in yeast.
    Genes Cells. 1999 Nov;4(11):619-25 PMID: 10620009
  35. A role for PML and the nuclear body in genomic stability.
    Oncogene. 1999 Dec 23;18(56):7941-7 PMID: 10637504
  36. Association of the Bloom syndrome protein with topoisomerase IIIalpha in somatic and meiotic cells.
    Cancer Res. 2000 Mar 1;60(5):1162-7 PMID: 10728666
  37. The Bloom's syndrome gene product interacts with topoisomerase III.
    J Biol Chem. 2000 Mar 31;275(13):9636-44 PMID: 10734115
  38. Bipartite structure of the SGS1 DNA helicase in Saccharomyces cerevisiae.
    Genetics. 2000 Mar;154(3):1101-14 PMID: 10757756
  39. The Bloom's syndrome gene product promotes branch migration of holliday junctions.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6504-8 PMID: 10823897
  40. MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae.
    Mol Gen Genet. 2000 Jun;263(5):812-27 PMID: 10905349
  41. Interaction between yeast sgs1 helicase and DNA topoisomerase III.
    J Biol Chem. 2000 Sep 1;275(35):26898-905 PMID: 10862619
  42. Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1.
    Mol Cell Biol. 2000 Dec;20(23):8758-66 PMID: 11073977
  43. Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae.
    Genetics. 2001 Jan;157(1):103-18 PMID: 11139495
  44. Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase.
    J Biol Chem. 2001 Mar 23;276(12):8848-55 PMID: 11124263
  45. Evidence for BLM and Topoisomerase IIIalpha interaction in genomic stability.
    Hum Mol Genet. 2001 Jun 1;10(12):1287-98 PMID: 11406610
  46. Historical overview: searching for replication help in all of the rec places.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8173-80 PMID: 11459950
  47. Participation of recombination proteins in rescue of arrested replication forks in UV-irradiated Escherichia coli need not involve recombination.
    Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8196-202 PMID: 11459953
  48. A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes.
    Proc Natl Acad Sci U S A. 1974 Nov;71(11):4508-12 PMID: 4140506
  49. Recombinationless meiosis in Saccharomyces cerevisiae.
    Mol Cell Biol. 1981 Oct;1(10):891-901 PMID: 7050657
  50. Use of T7 RNA polymerase to direct expression of cloned genes.
    Methods Enzymol. 1990;185:60-89 PMID: 2199796
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.932201
Published
2001-10-15
Pages
2730-40
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312806
Subset
IM
Grants
NIA NIH HHS · R01 AG016637-02 · United States
NIA NIH HHS · AG16637 · United States
External Links
PubMed source DOI: 10.1101/gad.932201 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2