Disruption of CHTF18 causes defective meiotic recombination in male mice.
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 devel...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002996&type=printable |
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| author | Karen M Berkowitz Aislinn R Sowash Lydia R Koenig Dawnette Urcuyo Fahmida Khan Fang Yang P Jeremy Wang Thomas A Jongens Klaus H Kaestner |
| author_facet | Karen M Berkowitz Aislinn R Sowash Lydia R Koenig Dawnette Urcuyo Fahmida Khan Fang Yang P Jeremy Wang Thomas A Jongens Klaus H Kaestner |
| author_sort | Karen M Berkowitz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a4f828a58af14df78693ac71a8bbb9b7 |
| institution | DOAJ |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-a4f828a58af14df78693ac71a8bbb9b72025-08-20T03:11:58ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-01811e100299610.1371/journal.pgen.1002996Disruption of CHTF18 causes defective meiotic recombination in male mice.Karen M BerkowitzAislinn R SowashLydia R KoenigDawnette UrcuyoFahmida KhanFang YangP Jeremy WangThomas A JongensKlaus H KaestnerCHTF18 (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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002996&type=printable |
| spellingShingle | Karen M Berkowitz Aislinn R Sowash Lydia R Koenig Dawnette Urcuyo Fahmida Khan Fang Yang P Jeremy Wang Thomas A Jongens Klaus H Kaestner Disruption of CHTF18 causes defective meiotic recombination in male mice. PLoS Genetics |
| title | Disruption of CHTF18 causes defective meiotic recombination in male mice. |
| title_full | Disruption of CHTF18 causes defective meiotic recombination in male mice. |
| title_fullStr | Disruption of CHTF18 causes defective meiotic recombination in male mice. |
| title_full_unstemmed | Disruption of CHTF18 causes defective meiotic recombination in male mice. |
| title_short | Disruption of CHTF18 causes defective meiotic recombination in male mice. |
| title_sort | disruption of chtf18 causes defective meiotic recombination in male mice |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002996&type=printable |
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