Home LiteratureArticle Details
PMID: 10525529 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RAD51 and DMC1 form mixed complexes associated with mouse meiotic chromosome cores and synaptonemal complexes.

The Journal of cell biology ·Vol. 147 ·No. 2 ·1999-10-18 ·Pages 207-20

Tarsounas M, Morita T, Pearlman RE, Moens PB

Abstract

The eukaryotic RecA homologues RAD51 and DMC1 function in homology recognition and formation of joint-molecule recombination intermediates during yeast meiosis. The precise immunolocalization of these two proteins on the meiotic chromosomes of plants and animals has been complicated by their high degree of identity at the amino acid level. With antibodies that have been immunodepleted of cross-reactive epitopes, we demonstrate that RAD51 and DMC1 have identical distribution patterns in extracts of mouse spermatocytes in successive prophase I stages, suggesting coordinate functionality. Immunofluorescence and immunoelectron microscopy with these antibodies demonstrate colocalization of the two proteins on the meiotic chromosome cores at early prophase I. We also show that mouse RAD51 and DMC1 establish protein-protein interactions with each other and with the chromosome core component COR1(SCP3) in a two-hybrid system and in vitro binding analyses. These results suggest that the formation of a multiprotein recombination complex associated with the meiotic chromosome cores is essential for the development and fulfillment of the meiotic recombination process.

MeSH Terms
Adenosine Triphosphatases Animals Cell Cycle Proteins DNA-Binding Proteins/genetics Immunohistochemistry Male Meiosis/genetics Mice Nuclear Proteins Phosphate-Binding Proteins Rad51 Recombinase Recombination, Genetic Spermatocytes/cytology,physiology
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Dmc1 protein, mouse Nuclear Proteins Phosphate-Binding Proteins Rad51 Recombinase Rad51 protein, mouse Adenosine Triphosphatases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tarsounas M
Department of Biology, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada.
Morita T
Pearlman R E
Moens P B
References (77)
77 references, click to expand
  1. Meiotic chromosome morphology and behavior in zip1 mutants of Saccharomyces cerevisiae.
    Genetics. 1998 Jun;149(2):817-32 PMID: 9611194
  2. The yeast Red1 protein localizes to the cores of meiotic chromosomes.
    J Cell Biol. 1997 Mar 10;136(5):957-67 PMID: 9060462
  3. Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma.
    Genes Dev. 1996 Oct 1;10(19):2411-22 PMID: 8843194
  4. Enzymes and molecular mechanisms of genetic recombination.
    Annu Rev Biochem. 1992;61:603-40 PMID: 1497320
  5. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  6. Heterochromatin, the synaptonemal complex and crossing over.
    J Cell Sci. 1984 Oct;71:159-76 PMID: 6520145
  7. DMC1 functions in a Saccharomyces cerevisiae meiotic pathway that is largely independent of the RAD51 pathway.
    Genetics. 1997 Oct;147(2):533-44 PMID: 9335591
  8. The human Rad51 protein: polarity of strand transfer and stimulation by hRP-A.
    EMBO J. 1997 Sep 1;16(17):5198-206 PMID: 9311980
  9. RecA homologs Dmc1 and Rad51 interact to form multiple nuclear complexes prior to meiotic chromosome synapsis.
    Cell. 1994 Dec 16;79(6):1081-92 PMID: 7528104
  10. The mouse and human homologs of DMC1, the yeast meiosis-specific homologous recombination gene, have a common unique form of exon-skipped transcript in meiosis.
    Nucleic Acids Res. 1996 Feb 1;24(3):470-7 PMID: 8602360
  11. DNA end-joining: from yeast to man.
    Trends Biochem Sci. 1998 Oct;23(10):394-8 PMID: 9810228
  12. A novel nucleic acid-binding protein that interacts with human rad51 recombinase.
    Nucleic Acids Res. 1997 Dec 15;25(24):4946-53 PMID: 9396801
  13. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53.
    Mol Cell Biol. 1996 Dec;16(12):7133-43 PMID: 8943369
  14. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.
    Nat Genet. 1996 Jul;13(3):336-42 PMID: 8673133
  15. Nuclear foci of mammalian recombination proteins are located at single-stranded DNA regions formed after DNA damage.
    Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1921-6 PMID: 10051570
  16. Human and mouse homologs of Schizosaccharomyces pombe rad1(+) and Saccharomyces cerevisiae RAD17: linkage to checkpoint control and mammalian meiosis.
    Genes Dev. 1998 Aug 15;12(16):2560-73 PMID: 9716408
  17. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.
    Mol Cell. 1998 Sep;2(3):317-28 PMID: 9774970
  18. Meiosis in asynaptic yeast.
    Genetics. 1990 Nov;126(3):563-74 PMID: 2249756
  19. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein.
    Cell. 1992 May 1;69(3):457-70 PMID: 1581961
  20. Correlation between pairing initiation sites, recombination nodules and meiotic recombination in Sordaria macrospora.
    Genetics. 1992 Sep;132(1):135-48 PMID: 1398050
  21. Partial rescue of the prophase I defects of Atm-deficient mice by p53 and p21 null alleles.
    Nat Genet. 1997 Dec;17(4):462-6 PMID: 9398851
  22. Organization of heterologous DNA inserts on the mouse meiotic chromosome core.
    Chromosoma. 1994 Oct;103(6):401-7 PMID: 7859560
  23. The yeast med1 mutant undergoes both meiotic homolog nondisjunction and precocious separation of sister chromatids.
    Genetics. 1994 Jan;136(1):65-74 PMID: 8138177
  24. ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis.
    Cell. 1993 Feb 12;72(3):365-78 PMID: 7916652
  25. Protein-protein interactions in the synaptonemal complex.
    Mol Biol Cell. 1997 Aug;8(8):1405-14 PMID: 9285814
  26. The synaptonemal complex protein SCP3 can form multistranded, cross-striated fibers in vivo.
    J Cell Biol. 1998 Jul 27;142(2):331-9 PMID: 9679134
  27. Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway.
    Cell. 1997 Sep 19;90(6):1123-35 PMID: 9323140
  28. Isolation and characterization of a yeast gene that is homologous with a meiosis-specific cDNA from a plant.
    Mol Gen Genet. 1993 Feb;237(1-2):225-32 PMID: 8455558
  29. Meiotic chromosomes: it takes two to tango.
    Genes Dev. 1997 Oct 15;11(20):2600-21 PMID: 9334324
  30. Rad51 immunocytology in rat and mouse spermatocytes and oocytes.
    Chromosoma. 1997 Sep;106(4):207-15 PMID: 9254722
  31. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis.
    Mol Cell. 1998 Apr;1(5):707-18 PMID: 9660954
  32. Organization of SCP1 protein molecules within synaptonemal complexes of the rat.
    Exp Cell Res. 1996 Jul 10;226(1):20-30 PMID: 8660935
  33. Targeted disruption of the Rad51 gene leads to lethality in embryonic mice.
    Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6236-40 PMID: 8692798
  34. Rad52 associates with RPA and functions with rad55 and rad57 to assemble meiotic recombination complexes.
    Genes Dev. 1998 Jul 15;12(14):2208-21 PMID: 9679065
  35. Crossover interference is abolished in the absence of a synaptonemal complex protein.
    Cell. 1994 Oct 21;79(2):283-92 PMID: 7954796
  36. RecA-like proteins are components of early meiotic nodules in lily.
    Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6868-73 PMID: 11038554
  37. A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes.
    EMBO J. 1992 Dec;11(13):5091-100 PMID: 1464329
  38. Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro.
    Cell. 1996 Nov 15;87(4):757-66 PMID: 8929543
  39. Localization of the N-terminus of SCP1 to the central element of the synaptonemal complex and evidence for direct interactions between the N-termini of SCP1 molecules organized head-to-head.
    Exp Cell Res. 1996 Jul 10;226(1):11-9 PMID: 8660934
  40. Cloning and sequence of the human RecA-like gene cDNA.
    Nucleic Acids Res. 1993 Apr 11;21(7):1665 PMID: 8479919
  41. Synaptonemal complex (SC) component Zip1 plays a role in meiotic recombination independent of SC polymerization along the chromosomes.
    Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9043-8 PMID: 8799151
  42. Purification and characterization of the human Rad51 protein, an analogue of E. coli RecA.
    EMBO J. 1994 Dec 1;13(23):5764-71 PMID: 7988572
  43. Homologous recombination and the roles of double-strand breaks.
    Trends Biochem Sci. 1995 Oct;20(10):387-91 PMID: 8533149
  44. The many interfaces of Mre11.
    Cell. 1998 Nov 25;95(5):583-6 PMID: 9845359
  45. Role of the human RAD51 protein in homologous recombination and double-stranded-break repair.
    Trends Biochem Sci. 1998 Jul;23(7):247-51 PMID: 9697414
  46. DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA.
    Cell. 1995 Aug 11;82(3):453-61 PMID: 7634335
  47. Saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination.
    Genes Cells. 1997 Oct;2(10):615-29 PMID: 9427283
  48. Meiosis: how could it work?
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8167-74 PMID: 8710842
  49. Fine structure of chromosome pairing in ten Ascomycetes: meiotic and premeiotic (mitotic) synaptonemal complexes.
    Chromosoma. 1973;40(4):401-16 PMID: 4693090
  50. Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I.
    Development. 1998 Oct;125(20):4007-17 PMID: 9735362
  51. The synaptonemal complex in genetic segregation.
    Annu Rev Genet. 1984;18:331-413 PMID: 6241453
  52. Centrifugal elutriation: separation of spermatogenic cells on the basis of sedimentation velocity.
    J Cell Physiol. 1975 Aug;86(1):177-89 PMID: 1236854
  53. Synaptonemal complex proteins: occurrence, epitope mapping and chromosome disjunction.
    J Cell Sci. 1994 Oct;107 ( Pt 10):2749-60 PMID: 7876343
  54. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression.
    Cell. 1992 May 1;69(3):439-56 PMID: 1581960
  55. 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
  56. Meiotic activation of rat pachytene spermatocytes with okadaic acid: the behaviour of synaptonemal complex components SYN1/SCP1 and COR1/SCP3.
    J Cell Sci. 1999 Feb;112 ( Pt 4):423-34 PMID: 9914155
  57. Localization of RecA-like recombination proteins on chromosomes of the lily at various meiotic stages.
    Genes Dev. 1995 Apr 15;9(8):925-34 PMID: 7774810
  58. The double-strand-break repair model for recombination.
    Cell. 1983 May;33(1):25-35 PMID: 6380756
  59. Distribution of the Rad51 recombinase in human and mouse spermatocytes.
    EMBO J. 1997 Sep 1;16(17):5207-15 PMID: 9311981
  60. Homotypic and heterotypic protein associations control Rad51 function in double-strand break repair.
    Genes Dev. 1994 Nov 1;8(21):2552-62 PMID: 7958917
  61. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog.
    Mol Cell. 1998 Apr;1(5):697-705 PMID: 9660953
  62. SCP2: a major protein component of the axial elements of synaptonemal complexes of the rat.
    Nucleic Acids Res. 1998 Jun 1;26(11):2572-9 PMID: 9592139
  63. Separation of spermatogenic cells and nuclei from rodent testes.
    Methods Cell Biol. 1977;15:15-54 PMID: 327197
  64. Recombination activities of HsDmc1 protein, the meiotic human homolog of RecA protein.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11221-6 PMID: 9326590
  65. The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes.
    Mol Cell Biol. 1994 Feb;14(2):1137-46 PMID: 8289794
  66. The fine structure of meiotic chromosome polarization and pairing in Locusta migratoria spermatocytes.
    Chromosoma. 1969;28(1):1-25 PMID: 5365542
  67. Roles for two RecA homologs in promoting meiotic chromosome synapsis.
    Genes Dev. 1995 Nov 1;9(21):2684-95 PMID: 7590245
  68. Association of BRCA1 with Rad51 in mitotic and meiotic cells.
    Cell. 1997 Jan 24;88(2):265-75 PMID: 9008167
  69. Structure and composition of synaptonemal complexes, isolated from rat spermatocytes.
    Eur J Cell Biol. 1985 Mar;36(2):307-14 PMID: 3996433
  70. Zip1-induced changes in synaptonemal complex structure and polycomplex assembly.
    J Cell Biol. 1995 Feb;128(4):455-66 PMID: 7860625
  71. Atm-deficient mice: a paradigm of ataxia telangiectasia.
    Cell. 1996 Jul 12;86(1):159-71 PMID: 8689683
  72. Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes.
    Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2958-63 PMID: 8610150
  73. Xrcc3 is required for assembly of Rad51 complexes in vivo.
    J Biol Chem. 1998 Aug 21;273(34):21482-8 PMID: 9705276
  74. The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes.
    Genes Dev. 1996 Oct 1;10(19):2423-37 PMID: 8843195
  75. Structural relationship of bacterial RecA proteins to recombination proteins from bacteriophage T4 and yeast.
    Science. 1993 Mar 26;259(5103):1892-6 PMID: 8456313
  76. A change in the phosphorylation pattern of the 30000-33000 Mr synaptonemal complex proteins of the rat between early and mid-pachytene.
    Chromosoma. 1995 Nov;104(3):154-63 PMID: 8529454
  77. A mouse homolog of the Escherichia coli recA and Saccharomyces cerevisiae RAD51 genes.
    Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6577-80 PMID: 8341671
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1999-10-18
Pages
207-20
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2174216
Subset
IM
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