The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice
Abstract
Breast tumor suppressor gene 1 (BRCA1) plays an essential role in maintaining genomic integrity. Here we show that mouse Brca1 is required for DNA-damage repair and crossing-over during spermatogenesis. MaleBrca1Δ11/Δ11p53+/- mice that carried a homozygous deletion of Brca1 exon 11 and a p53heterozygous mutation had significantly reduced testicular size and no spermatozoa in their seminiferous tubules. During spermatogenesis, homologous chromosomes from the mutant mice synapsed and advanced to the pachytene stage but failed to progress to the diplotene stage. Our analyses revealed that theBrca1 mutation affected cellular localization of several DNA damage-repair proteins. This included prolonged association of γH2AX with sites of DNA damage, reduced sex body formation, diminished Rad51 foci and absence of Mlh1 foci in the pachytene stage. Consequently, chromosomes from mutant mice did not form chiasmata, a point that connects exchanging homologous chromosomes. Brca1-mutant spermatocytes also exhibited decreased RNA expression levels of several genes that are involved in DNA-damage repair, including RuvB-like DNA helicase, XPB, p62 and TFIID. Of note, the premature termination of spermatogenesis at the pachytene stage was accompanied by increased apoptosis by both p53-dependent and p53-independent mechanisms. Thus, our study revealed an essential role of Brca1 in DNA-damage repair and crossing-over of homologous chromosomes during spermatogenesis.
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Cites
Genomic Instability in Mice Lacking Histone H2AX
Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., Reina-San-Martin, B., Coppola, V., Meffre, E., Difilippantonio, M. J., et al. (2002) · Science · doi:10.1126/science.1069398 · Cited by 1,385
Brca1 Controls Homology-Directed DNA Repair
Moynahan, M. E., Chiu, J. W., Koller, B. H., & Jasin, M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80202-6 · Cited by 1,245
Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., & Qin, J. (2000) · Genes & Development · doi:10.1101/gad.14.8.927 · Cited by 1,221 · cited 3×
“Consistent with this, a mass-spectrometry study showed that BRCA1 and other proteins, including MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11, NBS and RFC, form a complex called BRCA1-assocated genome-surveillance complex (BASC) (Wang et al., 2000) that is postulated to be involved in the recognition and repair of aberrant…”
BackgroundInfluentialCao, L., Li, W., Kim, S., Brodie, S. G., & Deng, C.-X. (2003) · Genes & Development · doi:10.1101/gad.1050003 · Cited by 293
Self-citationPaull, T. T., Cortez, D., Bowers, B., Elledge, S. J., & Gellert, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.111125998 · Cited by 282
Cited by
Biogenesis and germline functions of piRNAs
Klattenhoff, C., & Theurkauf, W. (2008) · Development · doi:10.1242/dev.006486 · Cited by 517
Hermo, L., Pelletier, R. ‐., Cyr, D. G., & Smith, C. E. (2010) · Microscopy Research and Technique · doi:10.1002/jemt.20783 · Cited by 422
Metadata
- Authors
- Xu, X., Aprelikova, O., Moens, P., Deng, C.-X., & Furth, P. A.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2003-05-01
- Volume
- 130
- Issue
- 9
- Pages
- 2001-2012
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2148598128
- Cited by
- 163
- References
- 5
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- closed
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- Xu, X., Aprelikova, O., Moens, P., Deng, C.-X., & Furth, P. A. (2003). Impaired meiotic DNA-damage repair and lack of crossing-over during spermatogenesis in BRCA1 full-length isoform deficient mice. Development. https://doi.org/10.1242/dev.00410
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