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PMID: 11238374 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

C. elegans mre-11 is required for meiotic recombination and DNA repair but is dispensable for the meiotic G(2) DNA damage checkpoint.

Genes & development ·Vol. 15 ·No. 5 ·2001-03-01 ·Pages 522-34

Chin GM, Villeneuve AM

Abstract

We investigated the roles of Caenorhabditis elegans MRE-11 in multiple cellular processes required to maintain genome integrity. Although yeast Mre11 is known to promote genome stability through several diverse pathways, inviability of vertebrate cells that lack Mre11 has hindered elucidation of the in vivo roles of this conserved protein in metazoan biology. Worms homozygous for an mre-11 null mutation are viable, allowing us to demonstrate in vivo requirements for MRE-11 in meiotic recombination and DNA repair. In mre-11 mutants, meiotic crossovers are not detected, and oocyte chromosomes lack chiasmata but appear otherwise intact. gamma-irradiation of mre-11 mutant germ cells during meiotic prophase eliminates progeny survivorship and induces chromosome fragmentation and other cytologically visible abnormalities, indicating a defect in repair of radiation-induced chromosome damage. Whereas mre-11 mutant germ cells are repair-deficient, they retain function of the meiotic G(2) DNA damage checkpoint that triggers germ cell apoptosis in response to ionizing radiation. Although mre-11/mre-11 animals derived from heterozygous parents are viable and produce many embryos, there is a marked drop both in the number and survivorship of embryos produced by succeeding generations. This progressive loss of fecundity and viability indicates that MRE-11 performs a function essential for maintaining reproductive capacity in the species.

MeSH Terms
Amino Acid Sequence Animals Caenorhabditis elegans/cytology,genetics,physiology Caenorhabditis elegans Proteins Cell Cycle Proteins/genetics,metabolism Chromosome Breakage Crossing Over, Genetic DNA Damage DNA Repair G2 Phase Gamma Rays Genes, cdc Helminth Proteins/genetics,metabolism In Situ Hybridization, Fluorescence Molecular Sequence Data Mutation Oocytes/cytology,metabolism Recombination, Genetic Sequence Homology, Amino Acid
Chemicals
Caenorhabditis elegans Proteins Cell Cycle Proteins Helminth Proteins mre-11 protein, C elegans
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chin G M
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305-5329, USA.
Villeneuve A M
References (60)
60 references, click to expand
  1. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  2. Partners and pathwaysrepairing a double-strand break.
    Trends Genet. 2000 Jun;16(6):259-64 PMID: 10827453
  3. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.
    Cell. 1998 May 1;93(3):467-76 PMID: 9590180
  4. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder.
    Cell. 1999 Dec 10;99(6):577-87 PMID: 10612394
  5. Alteration of N-terminal phosphoesterase signature motifs inactivates Saccharomyces cerevisiae Mre11.
    Genetics. 1998 Oct;150(2):591-600 PMID: 9755192
  6. Chromosome segregation during meiosis: building an unambivalent bivalent.
    Curr Top Dev Biol. 1998;37:263-99 PMID: 9352189
  7. The Caenorhabditis elegans sex determination gene mog-1 encodes a member of the DEAH-Box protein family.
    Mol Cell Biol. 1999 Mar;19(3):2189-97 PMID: 10022905
  8. In situ visualization of DNA double-strand break repair in human fibroblasts.
    Science. 1998 Apr 24;280(5363):590-2 PMID: 9554850
  9. Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination.
    Cell. 1990 May 4;61(3):419-36 PMID: 2185891
  10. The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance.
    Mol Cell Biol. 1999 Jan;19(1):556-66 PMID: 9858579
  11. Structural and functional similarities between the SbcCD proteins of Escherichia coli and the RAD50 and MRE11 (RAD32) recombination and repair proteins of yeast.
    Mol Microbiol. 1995 Sep;17(6):1215-7 PMID: 8594339
  12. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells.
    Nucleic Acids Res. 1997 Aug 1;25(15):2985-91 PMID: 9224597
  13. Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7186-91 PMID: 9207066
  14. MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans.
    Nature. 2000 Jan 13;403(6766):159-64 PMID: 10646593
  15. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing.
    EMBO J. 1998 Mar 16;17(6):1819-28 PMID: 9501103
  16. Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart.
    Annu Rev Genet. 1997;31:635-62 PMID: 9442910
  17. Repair of endonuclease-induced double-strand breaks in Saccharomyces cerevisiae: essential role for genes associated with nonhomologous end-joining.
    Genetics. 1999 Aug;152(4):1513-29 PMID: 10430580
  18. In-vitro recombination in rad and rnc mutants of Saccharomyces cerevisiae.
    Curr Genet. 1993 Jan;23(1):1-8 PMID: 8428378
  19. A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae.
    Cell. 1990 Jun 15;61(6):1089-101 PMID: 2190690
  20. Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest.
    Proc Natl Acad Sci U S A. 1996 May 14;93(10):4827-32 PMID: 8643488
  21. Alteration of telomeric sequences and senescence caused by mutations in RAD50 of Saccharomyces cerevisiae.
    Genes Cells. 1997 Jul;2(7):443-55 PMID: 9366550
  22. Disruption of mRad50 causes embryonic stem cell lethality, abnormal embryonic development, and sensitivity to ionizing radiation.
    Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7376-81 PMID: 10377422
  23. The 3' to 5' exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks.
    Mol Cell. 1998 Jun;1(7):969-79 PMID: 9651580
  24. A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites.
    Genetics. 1992 Jul;131(3):609-24 PMID: 1321065
  25. Mapping three-dimensional chromosome architecture in situ.
    Methods Cell Biol. 1998;53:187-233 PMID: 9348510
  26. Distinct roles of two separable in vitro activities of yeast Mre11 in mitotic and meiotic recombination.
    EMBO J. 1998 Nov 2;17(21):6412-25 PMID: 9799249
  27. Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products.
    Nature. 2000 May 25;405(6785):473-7 PMID: 10839544
  28. hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.
    Mol Cell Biol. 1997 Oct;17(10):6087-96 PMID: 9315668
  29. The Mre11-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Nov;19(11):7681-7 PMID: 10523656
  30. Increased ratio of targeted to random integration after transfection of chicken B cell lines.
    Cell. 1991 Oct 4;67(1):179-88 PMID: 1913816
  31. The many interfaces of Mre11.
    Cell. 1998 Nov 25;95(5):583-6 PMID: 9845359
  32. ATM-dependent phosphorylation of nibrin in response to radiation exposure.
    Nat Genet. 2000 May;25(1):115-9 PMID: 10802669
  33. Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae.
    Genetics. 1995 Apr;139(4):1521-32 PMID: 7789757
  34. The Mre11 complex and ATM: collaborating to navigate S phase.
    Curr Opin Cell Biol. 2000 Jun;12(3):293-6 PMID: 10801460
  35. Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells.
    EMBO J. 1999 Dec 1;18(23):6619-29 PMID: 10581236
  36. A global profile of germline gene expression in C. elegans.
    Mol Cell. 2000 Sep;6(3):605-16 PMID: 11030340
  37. Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast.
    Genetics. 1999 Nov;153(3):1271-83 PMID: 10545458
  38. Telomere maintenance is dependent on activities required for end repair of double-strand breaks.
    Curr Biol. 1998 May 21;8(11):657-60 PMID: 9635193
  39. mre11S--a yeast mutation that blocks double-strand-break processing and permits nonhomologous synapsis in meiosis.
    Genes Dev. 1997 Sep 1;11(17):2272-90 PMID: 9303542
  40. Complex formation and functional versatility of Mre11 of budding yeast in recombination.
    Cell. 1998 Nov 25;95(5):705-16 PMID: 9845372
  41. Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex.
    Genes Dev. 1999 May 15;13(10):1276-88 PMID: 10346816
  42. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway.
    Nature. 2000 Apr 6;404(6778):613-7 PMID: 10766245
  43. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.
    Genes Dev. 2000 Apr 15;14(8):927-39 PMID: 10783165
  44. Nondisjunction Mutants of the Nematode CAENORHABDITIS ELEGANS.
    Genetics. 1979 Jan;91(1):67-94 PMID: 17248881
  45. A novel mre11 mutation impairs processing of double-strand breaks of DNA during both mitosis and meiosis.
    Mol Cell Biol. 1998 Jan;18(1):260-8 PMID: 9418873
  46. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death.
    EMBO J. 1998 Jan 15;17(2):598-608 PMID: 9430650
  47. Mutations in XRS2 and RAD50 delay but do not prevent mating-type switching in Saccharomyces cerevisiae.
    Mol Cell Biol. 1994 May;14(5):3414-25 PMID: 8164689
  48. A cis-acting locus that promotes crossing over between X chromosomes in Caenorhabditis elegans.
    Genetics. 1994 Mar;136(3):887-902 PMID: 8005443
  49. Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95.
    J Biol Chem. 1998 Aug 21;273(34):21447-50 PMID: 9705271
  50. DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis.
    Oncogene. 1999 Dec 20;18(55):7883-99 PMID: 10630641
  51. Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae.
    Genetics. 1996 Mar;142(3):693-704 PMID: 8849880
  52. Caenorhabditis elegans msh-5 is required for both normal and radiation-induced meiotic crossing over but not for completion of meiosis.
    Genetics. 2000 Oct;156(2):617-30 PMID: 11014811
  53. Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage.
    Cell. 1998 Aug 7;94(3):399-409 PMID: 9708741
  54. Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae.
    Mol Cell Biol. 1996 May;16(5):2164-73 PMID: 8628283
  55. Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response.
    Science. 1999 Jul 30;285(5428):747-50 PMID: 10426999
  56. Identifying genes and proteins involved in human DNA repair processes using somatic cell and molecular genetics.
    Prog Clin Biol Res. 1996;395:175-99 PMID: 8895989
  57. A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell cycle arrest in C. elegans.
    Mol Cell. 2000 Mar;5(3):435-43 PMID: 10882129
  58. Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis.
    Cell. 1998 Aug 7;94(3):387-98 PMID: 9708740
  59. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response.
    Cell. 1998 May 1;93(3):477-86 PMID: 9590181
  60. DNA damage and checkpoint pathways: molecular anatomy and interactions with repair.
    Cell. 1998 Sep 4;94(5):555-8 PMID: 9741620
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.864101
Published
2001-03-01
Pages
522-34
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312651
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053804 · United States
NIGMS NIH HHS · GM-53804 · United States
External Links
PubMed source DOI: 10.1101/gad.864101 PMC Full Text View journal details
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