Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.
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.
Li
Xin Chenglin
XC
Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, New York, United States of America.
Li
Xin
X
Schimenti
John C
JC
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
D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C523791:Trip13 protein, mouse
Genesis. 2004 Nov;40(3):184-94
15515002
Nat Genet. 2005 Jan;37(1):41-7
15580272
Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):737-42
15640358
Exp Cell Res. 2004 May 15;296(1):57-63
15120994
Reproduction. 2004 May;127(5):569-80
15129012
Brief Bioinform. 2004 Jun;5(2):150-63
15260895
Chromosoma. 2004 Sep;113(3):126-36
15338235
EMBO J. 2004 Sep 1;23(17):3548-58
15297881
EMBO J. 1992 Dec;11(13):5091-100
1464329
Dev Genet. 1995;16(2):128-39
7736663
Cell. 2006 Mar 10;124(5):943-55
16530042
Curr Biol. 2006 Mar 21;16(6):R217-28
16546077
Dev Cell. 2006 Apr;10(4):521-9
16580996
Mol Reprod Dev. 2006 Aug;73(8):1061-72
16700071
Mech Dev. 2006 Jul;123(7):559-69
16822657
Genes Dev. 2006 Sep 15;20(18):2479-86
16980577
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14027-32
16968779
Nature. 2006 Nov 30;444(7119):624-8
17122775
Curr Biol. 2006 Dec 19;16(24):2473-9
17174924
J Biol Chem. 2007 Jun 15;282(24):17501-6
17446169
Nat Cell Biol. 1999 Oct;1(6):354-7
10559962
Mol Cell. 1999 Nov;4(5):805-14
10619027
Trends Genet. 2000 Sep;16(9):395-403
10973068
Mol Biol Cell. 2000 Oct;11(10):3601-15
11029058
Mutat Res. 2000 Nov 20;455(1-2):167-89
11113475
Nat Genet. 2001 Mar;27(3):271-6
11242108
Cell. 2001 Jul 13;106(1):47-57
11461701
Dev Cell. 2005 Jun;8(6):949-61
15935783
Chromosoma. 2005 Jul;114(2):127-34
15928951
Mol Cell Biol. 2005 Aug;25(16):7203-15
16055729
Cell. 2005 Sep 23;122(6):861-73
16179256
Mol Cell. 2005 Nov 23;20(4):563-73
16307920
Science. 2005 Dec 9;310(5754):1683-6
16339446
Mol Cell Biol. 2006 Feb;26(3):976-89
16428451
Methods Mol Biol. 2004;262:87-107
14769957
Mol Biol Cell. 2004 Apr;15(4):1568-79
14718568
PLoS Biol. 2004 Jan;2(1):E21
14737196
Cell. 2004 Apr 2;117(1):29-45
15066280
Cell. 2001 Jul 13;106(1):59-70
11461702
J Cell Sci. 2001 Aug;114(Pt 16):2953-65
11686299
Genetics. 2001 Dec;159(4):1511-25
11779793
Mol Cell. 2000 Nov;6(5):975-87
11106738
Mol Cell. 2000 Nov;6(5):989-98
11106739
J Cell Sci. 2002 Apr 15;115(Pt 8):1611-22
11950880
Science. 2002 May 10;296(5570):1115-8
12004129
Science. 2002 Jun 21;296(5576):2181-3
12077403
Nat Genet. 2002 Aug;31(4):385-90
12091911
J Exp Bot. 2003 Jan;54(380):25-38
12456752
Plant Cell. 2003 Jun;15(6):1281-95
12782723
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15706-11
14668445
Genetics. 2003 Dec;165(4):2283-7
14704203
Mol Endocrinol. 1995 Feb;9(2):243-54
7776974
Dev Biol. 1995 Jun;169(2):557-67
7781899
EMBO J. 1996 Jun 17;15(12):3006-15
8670802
Nature. 1996 Oct 31;383(6603):840-3
8893012
Genes Dev. 1997 Oct 15;11(20):2600-21
9334324
Nat Genet. 1997 Dec;17(4):457-61
9398850
Genetics. 1997 Dec;147(4):1545-56
9409820
Cell. 1998 Feb 6;92(3):401-13
9476899
Cell. 1998 May 1;93(3):349-59
9590170
Mol Cell. 1998 Apr;1(5):697-705
9660953
Genome Res. 1999 Jan;9(1):27-43
9927482
Genetics. 1999 Apr;151(4):1569-79
10101178
EMBO J. 1999 May 4;18(9):2648-58
10228176
Cell. 1999 Apr 30;97(3):313-24
10319812
Curr Biol. 2004 Dec 14;14(23):2135-42
15589157