Home LiteratureArticle Details
PMID: 16945961 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The role of AtMUS81 in DNA repair and its genetic interaction with the helicase AtRecQ4A.

Nucleic acids research ·Vol. 34 ·No. 16 ·2006-00-00 ·Pages 4438-48

Hartung F, Suer S, Bergmann T, Puchta H

Abstract

The endonuclease MUS81 has been shown in a variety of organisms to be involved in DNA repair in mitotic and meiotic cells. Homologues of the MUS81 gene exist in the genomes of all eukaryotes, pointing to a conserved role of the protein. However, the biological role of MUS81 varies between different eukaryotes. For example, while loss of the gene results in strongly impaired fertility in Saccharomyces cerevisiae and nearly complete sterility in Schizosaccharomyces pombe, it is not essential for meiosis in mammals. We identified a functional homologue (AtMUS81/At4g30870) in the genome of Arabidopsis thaliana and isolated a full-length cDNA of this gene. Analysing two independent T-DNA insertion lines of AtMUS81, we found that they are sensitive to the mutagens MMS and MMC. Both mutants have a deficiency in homologous recombination in somatic cells but only after induction by genotoxic stress. In contrast to yeast, no meiotic defect of AtMUS81 mutants was detectable and the mutants are viable. Crosses with a hyperrecombinogenic mutant of the AtRecQ4A helicase resulted in synthetic lethality in the double mutant. Thus, the nuclease AtMUS81 and the helicase AtRecQ4A seem to be involved in two alternative pathways of resolution of replicative DNA structures in somatic cells.

MeSH Terms
Amino Acid Sequence Arabidopsis/anatomy & histology,enzymology,genetics Arabidopsis Proteins/chemistry,genetics,physiology DNA Helicases/genetics DNA Repair Endonucleases/chemistry,genetics,physiology Molecular Sequence Data Mutagenesis, Insertional Open Reading Frames Phenotype Protein Structure, Tertiary Recombination, Genetic Sequence Alignment
Chemicals
Arabidopsis Proteins Endonucleases MUS81 protein, Arabidopsis DNA Helicases RecQ4A protein, Arabidopsis
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hartung F
Botanisches Institut II, Universität Karlsruhe, 76128 Karlsruhe, Germany.
Suer S
Bergmann T
Puchta H
References (61)
61 references, click to expand
  1. 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
  2. Crossover interference in Arabidopsis.
    Genetics. 2002 Apr;160(4):1631-9 PMID: 11973316
  3. Mus81-Eme1 and Rqh1 involvement in processing stalled and collapsed replication forks.
    J Biol Chem. 2002 Sep 6;277(36):32753-9 PMID: 12084712
  4. Holliday junction resolution in human cells: two junction endonucleases with distinct substrate specificities.
    EMBO J. 2002 Oct 15;21(20):5577-85 PMID: 12374758
  5. Recombinational repair and restart of damaged replication forks.
    Nat Rev Mol Cell Biol. 2002 Nov;3(11):859-70 PMID: 12415303
  6. Role of the AtRad1p endonuclease in homologous recombination in plants.
    EMBO Rep. 2002 Nov;3(11):1049-54 PMID: 12393748
  7. Intron gain and loss in the evolution of the conserved eukaryotic recombination machinery.
    Nucleic Acids Res. 2002 Dec 1;30(23):5175-81 PMID: 12466542
  8. Arabidopsis mutants sensitive to gamma radiation include the homologue of the human repair gene ERCC1.
    J Exp Bot. 2003 Feb;54(383):669-80 PMID: 12554710
  9. Cleavage of model replication forks by fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4.
    J Biol Chem. 2003 Feb 28;278(9):6928-35 PMID: 12473680
  10. Identification and characterization of human MUS81-MMS4 structure-specific endonuclease.
    J Biol Chem. 2003 Jun 13;278(24):21715-20 PMID: 12686547
  11. Identification and characterization of the human mus81-eme1 endonuclease.
    J Biol Chem. 2003 Jul 4;278(27):25172-8 PMID: 12721304
  12. Arabidopsis RecQsim, a plant-specific member of the RecQ helicase family, can suppress the MMS hypersensitivity of the yeast sgs1 mutant.
    Plant Mol Biol. 2003 May;52(2):273-84 PMID: 12856935
  13. Genome-wide insertional mutagenesis of Arabidopsis thaliana.
    Science. 2003 Aug 1;301(5633):653-7 PMID: 12893945
  14. The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism.
    Mol Cell. 2003 Sep;12(3):747-59 PMID: 14527419
  15. Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis.
    Mol Cell. 2003 Sep;12(3):761-74 PMID: 14527420
  16. Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cells.
    EMBO J. 2003 Nov 17;22(22):6137-47 PMID: 14609959
  17. The Bloom's syndrome helicase suppresses crossing over during homologous recombination.
    Nature. 2003 Dec 18;426(6968):870-4 PMID: 14685245
  18. RNA interference inhibition of Mus81 reduces mitotic recombination in human cells.
    Mol Biol Cell. 2004 Feb;15(2):552-62 PMID: 14617801
  19. The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions.
    Genes Dev. 2004 Jan 15;18(2):117-25 PMID: 14752007
  20. An Arabidopsis thaliana T-DNA mutagenized population (GABI-Kat) for flanking sequence tag-based reverse genetics.
    Plant Mol Biol. 2003 Sep;53(1-2):247-59 PMID: 14756321
  21. Interchromatid and interhomolog recombination in Arabidopsis thaliana.
    Plant Cell. 2004 Feb;16(2):342-52 PMID: 14729918
  22. Intrachromosomal homologous recombination in Arabidopsis thaliana.
    Methods Mol Biol. 2004;262:25-34 PMID: 14769954
  23. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis.
    Cell. 2004 Apr 2;117(1):29-45 PMID: 15066280
  24. Involvement of mammalian Mus81 in genome integrity and tumor suppression.
    Science. 2004 Jun 18;304(5678):1822-6 PMID: 15205536
  25. Structure and function of RecQ DNA helicases.
    Crit Rev Biochem Mol Biol. 2004 Mar-Apr;39(2):79-97 PMID: 15217989
  26. Roles of the AtErcc1 protein in recombination.
    Plant J. 2004 Aug;39(3):334-42 PMID: 15255863
  27. The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis.
    Genes Dev. 2004 Oct 15;18(20):2557-70 PMID: 15489296
  28. A model for replication repair in mammalian cells.
    J Mol Biol. 1976 Mar 5;101(3):417-25 PMID: 1255724
  29. At least six nucleotides preceding the AUG initiator codon enhance translation in mammalian cells.
    J Mol Biol. 1987 Aug 20;196(4):947-50 PMID: 3681984
  30. Intrachromosomal homologous recombination in whole plants.
    EMBO J. 1994 Jan 15;13(2):484-9 PMID: 8313893
  31. 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):253-60 PMID: 7736577
  32. The Bloom's syndrome gene product is homologous to RecQ helicases.
    Cell. 1995 Nov 17;83(4):655-66 PMID: 7585968
  33. Positional cloning of the Werner's syndrome gene.
    Science. 1996 Apr 12;272(5259):258-62 PMID: 8602509
  34. The helix-hairpin-helix DNA-binding motif: a structural basis for non-sequence-specific recognition of DNA.
    Nucleic Acids Res. 1996 Jul 1;24(13):2488-97 PMID: 8692686
  35. Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome.
    Nat Genet. 1999 May;22(1):82-4 PMID: 10319867
  36. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  37. The repair of double-strand breaks in plants: mechanisms and consequences for genome evolution.
    J Exp Bot. 2005 Jan;56(409):1-14 PMID: 15557293
  38. Mechanistically distinct roles for Sgs1p in checkpoint activation and replication fork maintenance.
    EMBO J. 2005 Jan 26;24(2):405-17 PMID: 15616582
  39. Differing requirements for the Arabidopsis Rad51 paralogs in meiosis and DNA repair.
    Plant J. 2005 Feb;41(4):533-45 PMID: 15686518
  40. The dual nature of homologous recombination in plants.
    Trends Genet. 2005 Mar;21(3):172-81 PMID: 15734576
  41. The HRDC domain of BLM is required for the dissolution of double Holliday junctions.
    EMBO J. 2005 Jul 20;24(14):2679-87 PMID: 15990871
  42. Disruption of murine Mus81 increases genomic instability and DNA damage sensitivity but does not promote tumorigenesis.
    Mol Cell Biol. 2005 Sep;25(17):7569-79 PMID: 16107704
  43. Arabidopsis RecQI4A suppresses homologous recombination and modulates DNA damage responses.
    Plant J. 2005 Sep;43(6):789-98 PMID: 16146519
  44. Making crossovers during meiosis.
    Biochem Soc Trans. 2005 Dec;33(Pt 6):1451-5 PMID: 16246144
  45. The RecQ gene family in plants.
    J Plant Physiol. 2006 Feb;163(3):287-96 PMID: 16371241
  46. The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast.
    Genetics. 2003 May;164(1):81-94 PMID: 12750322
  47. The importance of repairing stalled replication forks.
    Nature. 2000 Mar 2;404(6773):37-41 PMID: 10716434
  48. Replication fork arrest and DNA recombination.
    Trends Biochem Sci. 2000 Apr;25(4):173-8 PMID: 10754549
  49. AtRAD1, a plant homologue of human and yeast nucleotide excision repair endonucleases, is involved in dark repair of UV damages and recombination.
    Plant J. 2000 Mar;21(6):507-18 PMID: 10758501
  50. Crystal structure of the holliday junction DNA in complex with a single RuvA tetramer.
    Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8257-62 PMID: 10890893
  51. 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
  52. Nucleotide excision repair in yeast.
    Mutat Res. 2000 Jun 30;451(1-2):13-24 PMID: 10915862
  53. The Arabidopsis UVH1 gene is a homolog of the yeast repair endonuclease RAD1.
    Plant Physiol. 2000 Oct;124(2):579-86 PMID: 11027708
  54. Molecular characterisation of RecQ homologues in Arabidopsis thaliana.
    Nucleic Acids Res. 2000 Nov 1;28(21):4275-82 PMID: 11058127
  55. Damage tolerance protein Mus81 associates with the FHA1 domain of checkpoint kinase Cds1.
    Mol Cell Biol. 2000 Dec;20(23):8758-66 PMID: 11073977
  56. 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
  57. Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease.
    Genes Dev. 2001 Oct 15;15(20):2730-40 PMID: 11641278
  58. Mus81-Eme1 are essential components of a Holliday junction resolvase.
    Cell. 2001 Nov 16;107(4):537-48 PMID: 11719193
  59. Human Mus81-associated endonuclease cleaves Holliday junctions in vitro.
    Mol Cell. 2001 Nov;8(5):1117-27 PMID: 11741546
  60. A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae.
    Genetics. 2001 Dec;159(4):1511-25 PMID: 11779793
  61. Amplification of cDNA ends based on template-switching effect and step-out PCR.
    Nucleic Acids Res. 1999 Mar 15;27(6):1558-60 PMID: 10037822
Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/gkl576
Published
2006-00-00
Epub
2006-00-31
Pages
4438-48
Language
English
Region
England
NLM ID
0411011
PMCID
PMC1636358
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/gkl576 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