CHTF18 (chromosome transmission fidelity factor 18) is an evolutionarily conserved subunit of the Replication Factor C-like complex, CTF18-RLC. CHTF18 is necessary for the faithful passage of chromosomes from one daughter cell to the next during mitosis in yeast, and it is crucial for germline development in the fruitfly. Previously, we showed that mouse Chtf18 is expressed throughout the germline, suggesting a role for CHTF18 in mammalian gametogenesis. To determine the role of CHTF18 in mammalian germ cell development, we derived mice carrying null and conditional mutations in the Chtf18 gene. Chtf18-null males exhibit 5-fold decreased sperm concentrations compared to wild-type controls, resulting in subfertility. Loss of Chtf18 results in impaired spermatogenesis; spermatogenic cells display abnormal morphology, and the stereotypical arrangement of cells within seminiferous tubules is perturbed. Meiotic recombination is defective and homologous chromosomes separate prematurely during prophase I. Repair of DNA double-strand breaks is delayed and incomplete; both RAD51 and γH2AX persist in prophase I. In addition, MLH1 foci are decreased in pachynema. These findings demonstrate essential roles for CHTF18 in mammalian spermatogenesis and meiosis, and suggest that CHTF18 may function during the double-strand break repair pathway to promote the formation of crossovers.
Vyšlo v časopise: Disruption of Causes Defective Meiotic Recombination in Male Mice. PLoS Genet 8(11): e32767. doi:10.1371/journal.pgen.1002996 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002996
1. GuacciV, KoshlandD, StrunnikovA (1997) A direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiae. Cell 91 : 47–57.
2. LosadaA, HiranoM, HiranoT (1998) Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. Genes Dev 12 : 1986–1997.
3. MichaelisC, CioskR, NasmythK (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91 : 35–45.
4. DarwicheN, FreemanLA, StrunnikovA (1999) Characterization of the components of the putative mammalian sister chromatid cohesion complex. Gene 233 : 39–47.
5. GruberS, HaeringCH, NasmythK (2003) Chromosomal cohesin forms a ring. Cell 112 : 765–777.
6. UhlmannF (2004) The mechanism of sister chromatid cohesion. Exp Cell Res 296 : 80–85.
7. EijpeM, HeytingC, GrossB, JessbergerR (2000) Association of mammalian SMC1 and SMC3 proteins with meiotic chromosomes and synaptonemal complexes. J Cell Sci 113(Pt 4): 673–682.
8. RevenkovaE, JessbergerR (2006) Shaping meiotic prophase chromosomes: cohesins and synaptonemal complex proteins. Chromosoma 115 : 235–240.
9. YangF, WangPJ (2009) The Mammalian synaptonemal complex: a scaffold and beyond. Genome Dyn 5 : 69–80.
10. SujaJA, BarberoJL (2009) Cohesin complexes and sister chromatid cohesion in mammalian meiosis. Genome Dyn 5 : 94–116.
11. HandelMA, SchimentiJC (2010) Genetics of mammalian meiosis: regulation, dynamics and impact on fertility. Nat Rev Genet 11 : 124–136.
12. CohenPE, PollackSE, PollardJW (2006) Genetic analysis of chromosome pairing, recombination, and cell cycle control during first meiotic prophase in mammals. Endocr Rev 27 : 398–426.
13. LeeJY, Orr-WeaverTL (2001) The molecular basis of sister-chromatid cohesion. Annu Rev Cell Dev Biol 17 : 753–777.
14. RevenkovaE, JessbergerR (2005) Keeping sister chromatids together: cohesins in meiosis. Reproduction 130 : 783–790.
15. KimJ, MacNeillSA (2003) Genome stability: a new member of the RFC family. Curr Biol 13: R873–875.
16. KouprinaN, KrollE, KirillovA, BannikovV, ZakharyevV, et al. (1994) CHL12, a gene essential for the fidelity of chromosome transmission in the yeast Saccharomyces cerevisiae. Genetics 138 : 1067–1079.
17. HannaJS, KrollES, LundbladV, SpencerFA (2001) Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion. Mol Cell Biol 21 : 3144–3158.
18. MayerML, GygiSP, AebersoldR, HieterP (2001) Identification of RFC(Ctf18p, Ctf8p, Dcc1p): an alternative RFC complex required for sister chromatid cohesion in S. cerevisiae. Mol Cell 7 : 959–970.
19. JaffeAB, JongensTA (2001) Structure-specific abnormalities associated with mutations in a DNA replication accessory factor in Drosophila. Dev Biol 230 : 161–176.
20. MerkleCJ, KarnitzLM, Henry-SanchezJT, ChenJ (2003) Cloning and characterization of hCTF18, hCTF8, and hDCC1. Human homologs of a Saccharomyces cerevisiae complex involved in sister chromatid cohesion establishment. J Biol Chem 278 : 30051–30056.
21. OhtaS, ShiomiY, SugimotoK, ObuseC, TsurimotoT (2002) A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein. J Biol Chem 277 : 40362–40367.
22. ShiomiY, ShinozakiA, SugimotoK, UsukuraJ, ObuseC, et al. (2004) The reconstituted human Chl12-RFC complex functions as a second PCNA loader. Genes Cells 9 : 279–290.
23. BerkowitzKM, KaestnerKH, JongensTA (2008) Germline expression of mammalian CTF18, an evolutionarily conserved protein required for germ cell proliferation in the fly and sister chromatid cohesion in yeast. Mol Hum Reprod 14 : 143–150.
24. CullmannG, FienK, KobayashiR, StillmanB (1995) Characterization of the five replication factor C genes of Saccharomyces cerevisiae. Mol Cell Biol 15 : 4661–4671.
25. UhlmannF, CaiJ, GibbsE, O'DonnellM, HurwitzJ (1997) Deletion analysis of the large subunit p140 in human replication factor C reveals regions required for complex formation and replication activities. J Biol Chem 272 : 10058–10064.
26. UhlmannF, GibbsE, CaiJ, O'DonnellM, HurwitzJ (1997) Identification of regions within the four small subunits of human replication factor C required for complex formation and DNA replication. J Biol Chem 272 : 10065–10071.
27. LaksoM, PichelJG, GormanJR, SauerB, OkamotoY, et al. (1996) Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci U S A 93 : 5860–5865.
28. LomeliH, Ramos-MejiaV, GertsensteinM, LobeCG, NagyA (2000) Targeted insertion of Cre recombinase into the TNAP gene: excision in primordial germ cells. Genesis 26 : 116–117.
29. KanedaM, HirasawaR, ChibaH, OkanoM, LiE, et al. (2010) Genetic evidence for Dnmt3a-dependent imprinting during oocyte growth obtained by conditional knockout with Zp3-Cre and complete exclusion of Dnmt3b by chimera formation. Genes Cells
30. QiuMR, JiangL, MatthaeiKI, SchoenwaelderSM, KuffnerT, et al. (2010) Generation and characterization of mice with null mutation of the chloride intracellular channel 1 gene. Genesis 48 : 127–136.
31. YamaguchiS, KurimotoK, YabutaY, SasakiH, NakatsujiN, et al. (2009) Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. Development 136 : 4011–4020.
32. MaatoukDM, LovelandKL, McManusMT, MooreK, HarfeBD (2008) Dicer1 is required for differentiation of the mouse male germline. Biol Reprod 79 : 696–703.
33. MahadevaiahSK, TurnerJM, BaudatF, RogakouEP, de BoerP, et al. (2001) Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27 : 271–276.
34. AshleyT, PlugAW, XuJ, SolariAJ, ReddyG, et al. (1995) Dynamic changes in Rad51 distribution on chromatin during meiosis in male and female vertebrates. Chromosoma 104 : 19–28.
35. MoensPB, KolasNK, TarsounasM, MarconE, CohenPE, et al. (2002) 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 115 : 1611–1622.
36. PlugAW, PetersAH, KeeganKS, HoekstraMF, de BoerP, et al. (1998) Changes in protein composition of meiotic nodules during mammalian meiosis. J Cell Sci 111(Pt 4): 413–423.
37. BakerSM, PlugAW, ProllaTA, BronnerCE, HarrisAC, et al. (1996) Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet 13 : 336–342.
38. EdelmannW, CohenPE, KaneM, LauK, MorrowB, et al. (1996) Meiotic pachytene arrest in MLH1-deficient mice. Cell 85 : 1125–1134.
39. OgiwaraH, OhuchiT, UiA, TadaS, EnomotoT, et al. (2007) Ctf18 is required for homologous recombination-mediated double-strand break repair. Nucl Acids Res 35 : 4989–5000.
40. LengronneA, McIntyreJ, KatouY, KanohY, HopfnerKP, et al. (2006) Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. Mol Cell 23 : 787–799.
41. BylundGO, BurgersPM (2005) Replication protein A-directed unloading of PCNA by the Ctf18 cohesion establishment complex. Mol Cell Biol 25 : 5445–5455.
42. NaikiT, KondoT, NakadaD, MatsumotoK, SugimotoK (2001) Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway. Mol Cell Biol 21 : 5838–5845.
43. AnsbachAB, NoguchiC, KlansekIW, HeidlebaughM, NakamuraTM, et al. (2008) RFCCtf18 and the Swi1–Swi3 complex function in separate and redundant pathways required for the stabilization of replication forks to facilitate sister chromatid cohesion in Schizosaccharomyces pombe. Mol Biol Cell 19 : 595–607.
44. JessbergerR, ChuiG, LinnS, KemperB (1996) Analysis of the mammalian recombination protein complex RC-1. Mutat Res 350 : 217–227.
45. BuonomoSB, ClyneRK, FuchsJ, LoidlJ, UhlmannF, et al. (2000) Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. Cell 103 : 387–398.
46. LeeJ, IwaiT, YokotaT, YamashitaM (2003) Temporally and spatially selective loss of Rec8 protein from meiotic chromosomes during mammalian meiosis. J Cell Sci 116 : 2781–2790.
47. LeeJ, OkadaK, OgushiS, MiyanoT, MiyakeM, et al. (2006) Loss of Rec8 from chromosome arm and centromere region is required for homologous chromosome separation and sister chromatid separation, respectively, in mammalian meiosis. Cell Cycle 5 : 1448–1455.
48. BuaasFW, KirshAL, SharmaM, McLeanDJ, MorrisJL, et al. (2004) Plzf is required in adult male germ cells for stem cell self-renewal. Nat Genet 36 : 647–652.
49. PetronczkiM, SiomosMF, NasmythK (2003) Un menage a quatre: the molecular biology of chromosome segregation in meiosis. Cell 112 : 423–440.
50. XuH, BeasleyMD, WarrenWD, van der HorstGT, McKayMJ (2005) Absence of mouse REC8 cohesin promotes synapsis of sister chromatids in meiosis. Dev Cell 8 : 949–961.
51. LightfootJ, TestoriS, BarrosoC, Martinez-PerezE (2011) Loading of meiotic cohesin by SCC-2 is required for early processing of DSBs and for the DNA damage checkpoint. Curr Biol 21 : 1421–1430.
52. SonodaE, MatsusakaT, MorrisonC, VagnarelliP, HoshiO, et al. (2001) Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev Cell 1 : 759–770.
53. PottsPR, PorteusMH, YuH (2006) Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. Embo J 25 : 3377–3388.
54. SchmitzJ, WatrinE, LenartP, MechtlerK, PetersJM (2007) Sororin is required for stable binding of cohesin to chromatin and for sister chromatid cohesion in interphase. Curr Biol 17 : 630–636.
55. Bekker-JensenS, LukasC, KitagawaR, MelanderF, KastanMB, et al. (2006) Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol 173 : 195–206.
56. WatrinE, PetersJM (2009) The cohesin complex is required for the DNA damage-induced G2/M checkpoint in mammalian cells. Embo J 28 : 2625–2635.
57. KimJS, KrasievaTB, LaMorteV, TaylorAM, YokomoriK (2002) Specific recruitment of human cohesin to laser-induced DNA damage. J Biol Chem 277 : 45149–45153.
58. BermudezVP, ManiwaY, TappinI, OzatoK, YokomoriK, et al. (2003) The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNA. Proc Natl Acad Sci U S A 100 : 10237–10242.
59. TerretME, SherwoodR, RahmanS, QinJ, JallepalliPV (2009) Cohesin acetylation speeds the replication fork. Nature 462 : 231–234.
60. RyuMJ, KimBJ, LeeJW, LeeMW, ChoiHK, et al. (2006) Direct interaction between cohesin complex and DNA replication machinery. Biochem Biophys Res Commun 341 : 770–775.
61. RevenkovaE, EijpeM, HeytingC, HodgesCA, HuntPA, et al. (2004) Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination. Nat Cell Biol 6 : 555–562.
62. BannisterLA, ReinholdtLG, MunroeRJ, SchimentiJC (2004) Positional cloning and characterization of mouse mei8, a disrupted allelle of the meiotic cohesin Rec8. Genesis 40 : 184–194.
63. KolasNK, MarconE, CrackowerMA, HoogC, PenningerJM, et al. (2005) Mutant meiotic chromosome core components in mice can cause apparent sexual dimorphic endpoints at prophase or X-Y defective male-specific sterility. Chromosoma 114 : 92–102.
64. PetersAH, PlugAW, van VugtMJ, de BoerP (1997) A drying-down technique for the spreading of mammalian meiocytes from the male and female germline. Chromosome Res 5 : 66–68.
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