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PMID: 15937223 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation.

Genes & development ·Vol. 19 ·No. 11 ·2005-06-01 ·Pages 1376-89

de Vries FA, de Boer E, van den Bosch M, Baarends WM, Ooms M, Yuan L, Liu JG, van Zeeland AA, Heyting C, Pastink A

Abstract

In meiotic prophase, synaptonemal complexes (SCs) closely appose homologous chromosomes (homologs) along their length. SCs are assembled from two axial elements (AEs), one along each homolog, which are connected by numerous transverse filaments (TFs). We disrupted the mouse gene encoding TF protein Sycp1 to analyze the role of TFs in meiotic chromosome behavior and recombination. Sycp1(-/-) mice are infertile, but otherwise healthy. Sycp1(-/-) spermatocytes form normal AEs, which align homologously, but do not synapse. Most Sycp1(-/-) spermatocytes arrest in pachynema, whereas a small proportion reaches diplonema, or, exceptionally, metaphase I. In leptotene Sycp1(-/-) spermatocytes, gammaH2AX (indicative of DNA damage, including double-strand breaks) appears normal. In pachynema, Sycp1(-/-) spermatocytes display a number of discrete gammaH2AX domains along each chromosome, whereas gammaH2AX disappears from autosomes in wild-type spermatocytes. RAD51/DMC1, RPA, and MSH4 foci (which mark early and intermediate steps in pairing/recombination) appear in similar numbers as in wild type, but do not all disappear, and MLH1 and MLH3 foci (which mark late steps in crossing over) are not formed. Crossovers were rare in metaphase I of Sycp1(-/-) mice. We propose that SYCP1 has a coordinating role, and ensures formation of crossovers. Unexpectedly, Sycp1(-/-) spermatocytes did not form XY bodies.

MeSH Terms
Animals Apoptosis Base Sequence Crossing Over, Genetic DNA Primers DNA-Binding Proteins Female In Situ Nick-End Labeling Infertility, Female/genetics Infertility, Male/genetics Male Meiosis/physiology Mice Mice, Knockout Nuclear Proteins/genetics,physiology Recombination, Genetic/physiology Spermatocytes/cytology Synaptonemal Complex/ultrastructure
Chemicals
DNA Primers DNA-Binding Proteins Nuclear Proteins Sycp1 protein, mouse
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
de Vries Femke A T
Department of Toxicogenetics, Leiden University Medical Centre, The Netherlands.
de Boer Esther
van den Bosch Mike
Baarends Willy M
Ooms Marja
Yuan Li
Liu Jian-Guo
van Zeeland Albert A
Heyting Christa
Pastink Albert
References (56)
56 references, click to expand
  1. Specific arrests of spermatogenesis in genetically modified and mutant mice.
    Cytogenet Genome Res. 2003;103(3-4):267-76 PMID: 15051947
  2. c(3)G encodes a Drosophila synaptonemal complex protein.
    Genes Dev. 2001 Dec 1;15(23):3130-43 PMID: 11731477
  3. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae.
    Microbiol Mol Biol Rev. 1999 Jun;63(2):349-404 PMID: 10357855
  4. Localization and roles of Ski8p protein in Sordaria meiosis and delineation of three mechanistically distinct steps of meiotic homolog juxtaposition.
    Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12865-70 PMID: 14563920
  5. Meiotic cells monitor the status of the interhomolog recombination complex.
    Genes Dev. 1997 Jan 1;11(1):106-18 PMID: 9000054
  6. Meiotic chromosomes: integrating structure and function.
    Annu Rev Genet. 1999;33:603-754 PMID: 10690419
  7. The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination.
    J Cell Sci. 2002 Apr 15;115(Pt 8):1611-22 PMID: 11950880
  8. The single-end invasion: an asymmetric intermediate at the double-strand break to double-holliday junction transition of meiotic recombination.
    Cell. 2001 Jul 13;106(1):59-70 PMID: 11461702
  9. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.
    Nat Genet. 1996 Jul;13(3):336-42 PMID: 8673133
  10. Localisation of RAD50 and MRE11 in spermatocyte nuclei of mouse and rat.
    Chromosoma. 2000;109(1-2):123-32 PMID: 10855503
  11. hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes.
    Mol Cell. 2004 Aug 13;15(3):437-51 PMID: 15304223
  12. Megabase chromatin domains involved in DNA double-strand breaks in vivo.
    J Cell Biol. 1999 Sep 6;146(5):905-16 PMID: 10477747
  13. Roles of RecA homologues Rad51 and Dmc1 during meiotic recombination.
    Cytogenet Genome Res. 2004;107(3-4):201-7 PMID: 15467365
  14. MSH4 acts in conjunction with MLH1 during mammalian meiosis.
    FASEB J. 2000 Aug;14(11):1539-47 PMID: 10928988
  15. Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3.
    J Cell Biol. 2003 Mar 3;160(5):657-70 PMID: 12615909
  16. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis.
    Nat Genet. 1999 Jan;21(1):123-7 PMID: 9916805
  17. Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans.
    Genes Dev. 2002 Sep 15;16(18):2428-42 PMID: 12231631
  18. Meiotic chromosome preparation and protein labeling.
    Methods Cell Biol. 1991;35:177-202 PMID: 1779856
  19. 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
  20. Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis.
    Genes Dev. 1999 Mar 1;13(5):523-31 PMID: 10072381
  21. ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis.
    Cell. 1993 Feb 12;72(3):365-78 PMID: 7916652
  22. Recombinational DNA double-strand breaks in mice precede synapsis.
    Nat Genet. 2001 Mar;27(3):271-6 PMID: 11242108
  23. Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis.
    Mol Hum Reprod. 2004 Dec;10(12):917-24 PMID: 15489243
  24. Squash procedure for protein immunolocalization in meiotic cells.
    Chromosome Res. 1998 Dec;6(8):639-42 PMID: 10099877
  25. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis.
    Mol Cell. 1998 Apr;1(5):707-18 PMID: 9660954
  26. 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
  27. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice.
    Genes Dev. 2000 May 1;14(9):1085-97 PMID: 10809667
  28. Male mouse recombination maps for each autosome identified by chromosome painting.
    Am J Hum Genet. 2002 Dec;71(6):1353-68 PMID: 12432495
  29. A coiled-coil related protein specific for synapsed regions of meiotic prophase chromosomes.
    EMBO J. 1992 Dec;11(13):5091-100 PMID: 1464329
  30. Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis.
    Genes Dev. 1997 Jun 15;11(12):1573-82 PMID: 9203583
  31. Meiotic arrest and aneuploidy in MLH3-deficient mice.
    Nat Genet. 2002 Aug;31(4):385-90 PMID: 12091911
  32. 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
  33. cDNA sequence of the murine synaptonemal complex protein 1 (SCP1).
    Biochim Biophys Acta. 1995 Sep 19;1263(3):258-60 PMID: 7548215
  34. Loss of HR6B ubiquitin-conjugating activity results in damaged synaptonemal complex structure and increased crossing-over frequency during the male meiotic prophase.
    Mol Cell Biol. 2003 Feb;23(4):1151-62 PMID: 12556476
  35. BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation.
    Curr Biol. 2004 Dec 14;14(23):2135-42 PMID: 15589157
  36. Extensive 3'-overhanging, single-stranded DNA associated with the meiosis-specific double-strand breaks at the ARG4 recombination initiation site.
    Cell. 1991 Mar 22;64(6):1155-61 PMID: 2004421
  37. Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays.
    Cancer Res. 1993 Apr 15;53(8):1945-51 PMID: 8467513
  38. A drying-down technique for the spreading of mammalian meiocytes from the male and female germline.
    Chromosome Res. 1997 Feb;5(1):66-8 PMID: 9088645
  39. 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
  40. The genetics and molecular biology of the synaptonemal complex.
    Annu Rev Cell Dev Biol. 2004;20:525-58 PMID: 15473851
  41. Functional specificity of MutL homologs in yeast: evidence for three Mlh1-based heterocomplexes with distinct roles during meiosis in recombination and mismatch correction.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13914-9 PMID: 10570173
  42. Synaptonemal complexities and commonalities.
    Mol Cell. 2003 Sep;12(3):533-5 PMID: 14527398
  43. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
    J Cell Biol. 1992 Nov;119(3):493-501 PMID: 1400587
  44. 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
  45. 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
  46. Genetic control of mammalian meiotic recombination. I. Variation in exchange frequencies among males from inbred mouse strains.
    Genetics. 2002 Sep;162(1):297-306 PMID: 12242241
  47. Mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis.
    Exp Cell Res. 2004 May 15;296(1):71-9 PMID: 15120996
  48. ATM and RPA in meiotic chromosome synapsis and recombination.
    Nat Genet. 1997 Dec;17(4):457-61 PMID: 9398850
  49. Relationship of DNA double-strand breaks to synapsis in Drosophila.
    J Cell Sci. 2003 Aug 1;116(Pt 15):3069-77 PMID: 12799415
  50. Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination.
    Dev Cell. 2003 Sep;5(3):463-74 PMID: 12967565
  51. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction.
    Cell. 1994 Dec 16;79(6):1069-80 PMID: 8001134
  52. Caught in the act: deducing meiotic function from protein immunolocalization.
    Curr Top Dev Biol. 1998;37:201-39 PMID: 9352187
  53. Induced premature G2/M-phase transition in pachytene spermatocytes includes events unique to meiosis.
    Dev Biol. 1995 Jun;169(2):557-67 PMID: 7781899
  54. The mouse "tool box" for meiotic studies.
    Cytogenet Genome Res. 2004;105(2-4):166-71 PMID: 15237204
  55. Genetic and cytological characterization of the recombination protein RAD-51 in Caenorhabditis elegans.
    Chromosoma. 2003 Jul;112(1):6-16 PMID: 12684824
  56. The budding yeast Msh4 protein functions in chromosome synapsis and the regulation of crossover distribution.
    Genetics. 2001 Jul;158(3):1013-25 PMID: 11454751
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.329705
Published
2005-06-01
Pages
1376-89
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1142560
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.329705 PMC Full Text View journal details
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