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Journal article
Disruption of Chtf18 Causes Defective Meiotic Recombination in Male Mice
PLoS genetics, v 8(11), pp e1002996-e1002996
01 Nov 2012
PMID: 23133398
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 cH2AX 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.
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Details
- Title
- Disruption of Chtf18 Causes Defective Meiotic Recombination in Male Mice
- Creators
- Karen M. Berkowitz - Drexel UniversityAislinn R. Sowash - Drexel UniversityLydia R. Koenig - Drexel UniversityDawnette Urcuyo - Drexel UniversityFahmida Khan - Drexel UniversityFang Yang - University of PennsylvaniaP. Jeremy Wang - University of PennsylvaniaThomas A. Jongens - University of PennsylvaniaKlaus H. Kaestner - University of Pennsylvania
- Publication Details
- PLoS genetics, v 8(11), pp e1002996-e1002996
- Publisher
- Public Library Science
- Number of pages
- 15
- Grant note
- HD 01256; HD 34449; HD 33834; GM076327; P01-CA082710 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P01CA082710 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01GM106262 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) U54HD034449 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) P30 DK 50306 / NIH at the University of Pennsylvania School of Medicine P30DK050306 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) K12HD001256 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000311891600005
- Scopus ID
- 2-s2.0-84870692929
- Other Identifier
- 991019168244904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity