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Publication : Characterization of Spo11-dependent and independent phospho-H2AX foci during meiotic prophase I in the male mouse.

First Author  Chicheportiche A Year  2007
Journal  J Cell Sci Volume  120
Issue  Pt 10 Pages  1733-42
PubMed ID  17456548 Mgi Jnum  J:124198
Mgi Id  MGI:3721023 Doi  10.1242/jcs.004945
Citation  Chicheportiche A, et al. (2007) Characterization of Spo11-dependent and independent phospho-H2AX foci during meiotic prophase I in the male mouse. J Cell Sci 120(Pt 10):1733-42
abstractText  Meiotic DNA double strand breaks (DSBs) are indicated at leptotene by the phosphorylated form of histone H2AX (gamma-H2AX). In contrast to previous studies, we identified on both zygotene and pachytene chromosomes two distinct types of gamma-H2AX foci: multiple small (S) foci located along autosomal synaptonemal complexes (SCs) and larger signals on chromatin loops (L-foci). The S-foci number gradually declined throughout pachytene, in parallel with the repair of DSBs monitored by repair proteins suggesting that S-foci mark DSB repair events. We validated this interpretation by showing the absence of S-foci in Spo11(-/-) spermatocytes. By contrast, the L-foci number was very low through pachytene. Based on the analysis of gamma-H2AX labeling after irradiation of spermatocytes, the formation of DSBs clearly induced L-foci formation. Upon DSB repair, these foci appear to be processed and lead to the above mentioned S-foci. The presence of L-foci in wild-type pachytene and diplotene could therefore reflect delayed or unregulated DSB repair events. Interestingly, their distribution was different in Spo11(+/-) spermatocytes compared with Spo11(+/+) spermatocytes, where DSB repair might be differently regulated as a response to homeostatic control of crossing-over. The presence of these L-foci in Spo11(-/-) spermatocytes raises the interesting possibility of yet uncharacterized alterations in DNA or chromosome structure in Spo11(-/-) cells.
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