Journal
REPRODUCTIVE BIOMEDICINE ONLINE
Volume 18, Issue 1, Pages 37-44Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S1472-6483(10)60422-1
Keywords
asynapsis; ATR; BRCA1; gamma H2AX; meiosis; oocyte
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Funding
- Agencia de Gestio d'Ajuts Universitaris i Cie Recerca Cie la Generalitat de Catalunya [2004FI00953]
- Fondo de Investigacion Sanitaria [FIS 02/0297]
- Universtitat Autonoma Cie Barcelona [PRP2006-02]
- Ministerio de Ciencia y Tecnologia [BFU2006-1295]
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Asynapsis of homologous chromosomes at the pachytene stage has been associated with gametogenic failure and infertility, but the cellular mechanisms involved are currently unknown ill human meiocytes. In mice, the protein encoded by the breast-cancer susceptibility gene Brca1 has been described to direct kinase ATR (ataxia telangiectasia and Rad3 related) to any unpaired DNA at the pachytene stage, where ATR triggers H2AX phosphorylation, resulting in the silencing of those chromosomes. In this study, the distribution of ATR, BRCA1 and the phosphorylated histone gamma H2AX is assessed by immunofluorescence in human oocytes and it is found that they localize at unpaired chromosomes at the pachytene stage. Evidence is shown to propose that BRCA1, ATR and gamma H2AX in the human may be part of a system Such as the one previously described in mouse. which signals unsynapsed chromosomes at pachytene and may lead to their silencing.
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