title: Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.
abstract: In mammalian meiosis, homologous chromosome synapsis is coupled with recombination. As in most eukaryotes, mammalian meiocytes have checkpoints that monitor the fidelity of these processes. We report that the mouse ortholog (Trip13) of pachytene checkpoint 2 (PCH2), an essential component of the synapsis checkpoint in Saccharomyces cerevisiae and Caenorhabditis elegans, is required for completion of meiosis in both sexes. TRIP13-deficient mice exhibit spermatocyte death in pachynema and loss of oocytes around birth. The chromosomes of mutant spermatocytes synapse fully, yet retain several markers of recombination intermediates, including RAD51, BLM, and RPA. These chromosomes also exhibited the chiasmata markers MLH1 and MLH3, and okadaic acid treatment of mutant spermatocytes caused progression to metaphase I with bivalent chromosomes. Double mutant analysis demonstrated that the recombination and synapsis genes Spo11, Mei1, Rec8, and Dmc1 are all epistatic to Trip13, suggesting that TRIP13 does not have meiotic checkpoint function in mice. Our data indicate that TRIP13 is required after strand invasion for completing a subset of recombination events, but possibly not those destined to be crossovers. To our knowledge, this is the first model to separate recombination defects from asynapsis in mammalian meiosis, and provides the first evidence that unrepaired DNA damage alone can trigger the pachytene checkpoint response in mice.
authors: Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, New York, United States of America.
authors: Xin Chenglin
authors: XC
authors: Li
authors: Xin
authors: X
authors: Li
authors: John C
authors: JC
authors: Schimenti
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D023902:Chromosome Pairing / Q000235:genetics*; D002875:Chromosomes / Q000737:chemistry; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018816:Genes, cdc / Q000502:physiology*; D007246:Infertility / Q000235:genetics; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D010053:Ovary / Q000378:metabolism; D049471:Pachytene Stage / Q000235:genetics; D010802:Phylogeny; D011995:Recombination, Genetic / Q000235:genetics*; D013090:Spermatocytes / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C523791:Trip13 protein, mouse
references: Genesis. 2004 Nov;40(3):184-94
references: 15515002
references: Nat Genet. 2005 Jan;37(1):41-7
references: 15580272
references: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):737-42
references: 15640358
references: Exp Cell Res. 2004 May 15;296(1):57-63
references: 15120994
references: Reproduction. 2004 May;127(5):569-80
references: 15129012
references: Brief Bioinform. 2004 Jun;5(2):150-63
references: 15260895
references: Chromosoma. 2004 Sep;113(3):126-36
references: 15338235
references: EMBO J. 2004 Sep 1;23(17):3548-58
references: 15297881
references: EMBO J. 1992 Dec;11(13):5091-100
references: 1464329
references: Dev Genet. 1995;16(2):128-39
references: 7736663
references: Cell. 2006 Mar 10;124(5):943-55
references: 16530042
references: Curr Biol. 2006 Mar 21;16(6):R217-28
references: 16546077
references: Dev Cell. 2006 Apr;10(4):521-9
references: 16580996
references: Mol Reprod Dev. 2006 Aug;73(8):1061-72
references: 16700071
references: Mech Dev. 2006 Jul;123(7):559-69
references: 16822657
references: Genes Dev. 2006 Sep 15;20(18):2479-86
references: 16980577
references: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14027-32
references: 16968779
references: Nature. 2006 Nov 30;444(7119):624-8
references: 17122775
references: Curr Biol. 2006 Dec 19;16(24):2473-9
references: 17174924
references: J Biol Chem. 2007 Jun 15;282(24):17501-6
references: 17446169
references: Nat Cell Biol. 1999 Oct;1(6):354-7
references: 10559962
references: Mol Cell. 1999 Nov;4(5):805-14
references: 10619027
references: Trends Genet. 2000 Sep;16(9):395-403
references: 10973068
references: Mol Biol Cell. 2000 Oct;11(10):3601-15
references: 11029058
references: Mutat Res. 2000 Nov 20;455(1-2):167-89
references: 11113475
references: Nat Genet. 2001 Mar;27(3):271-6
references: 11242108
references: Cell. 2001 Jul 13;106(1):47-57
references: 11461701
references: Dev Cell. 2005 Jun;8(6):949-61
references: 15935783
references: Chromosoma. 2005 Jul;114(2):127-34
references: 15928951
references: Mol Cell Biol. 2005 Aug;25(16):7203-15
references: 16055729
references: Cell. 2005 Sep 23;122(6):861-73
references: 16179256
references: Mol Cell. 2005 Nov 23;20(4):563-73
references: 16307920
references: Science. 2005 Dec 9;310(5754):1683-6
references: 16339446
references: Mol Cell Biol. 2006 Feb;26(3):976-89
references: 16428451
references: Methods Mol Biol. 2004;262:87-107
references: 14769957
references: Mol Biol Cell. 2004 Apr;15(4):1568-79
references: 14718568
references: PLoS Biol. 2004 Jan;2(1):E21
references: 14737196
references: Cell. 2004 Apr 2;117(1):29-45
references: 15066280
references: Cell. 2001 Jul 13;106(1):59-70
references: 11461702
references: J Cell Sci. 2001 Aug;114(Pt 16):2953-65
references: 11686299
references: Genetics. 2001 Dec;159(4):1511-25
references: 11779793
references: Mol Cell. 2000 Nov;6(5):975-87
references: 11106738
references: Mol Cell. 2000 Nov;6(5):989-98
references: 11106739
references: J Cell Sci. 2002 Apr 15;115(Pt 8):1611-22
references: 11950880
references: Science. 2002 May 10;296(5570):1115-8
references: 12004129
references: Science. 2002 Jun 21;296(5576):2181-3
references: 12077403
references: Nat Genet. 2002 Aug;31(4):385-90
references: 12091911
references: J Exp Bot. 2003 Jan;54(380):25-38
references: 12456752
references: Plant Cell. 2003 Jun;15(6):1281-95
references: 12782723
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15706-11
references: 14668445
references: Genetics. 2003 Dec;165(4):2283-7
references: 14704203
references: Mol Endocrinol. 1995 Feb;9(2):243-54
references: 7776974
references: Dev Biol. 1995 Jun;169(2):557-67
references: 7781899
references: EMBO J. 1996 Jun 17;15(12):3006-15
references: 8670802
references: Nature. 1996 Oct 31;383(6603):840-3
references: 8893012
references: Genes Dev. 1997 Oct 15;11(20):2600-21
references: 9334324
references: Nat Genet. 1997 Dec;17(4):457-61
references: 9398850
references: Genetics. 1997 Dec;147(4):1545-56
references: 9409820
references: Cell. 1998 Feb 6;92(3):401-13
references: 9476899
references: Cell. 1998 May 1;93(3):349-59
references: 9590170
references: Mol Cell. 1998 Apr;1(5):697-705
references: 9660953
references: Genome Res. 1999 Jan;9(1):27-43
references: 9927482
references: Genetics. 1999 Apr;151(4):1569-79
references: 10101178
references: EMBO J. 1999 May 4;18(9):2648-58
references: 10228176
references: Cell. 1999 Apr 30;97(3):313-24
references: 10319812
references: Curr Biol. 2004 Dec 14;14(23):2135-42
references: 15589157