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Distribution of DNA damage in the human sperm nucleus

Human sperm chromatin contains two structural domains commonly considered as susceptible to DNA damage: the nucleosomal domain, associated with histones and the MAR domain, associated with nuclear matrix proteins. Using a qPCR approach, we demonstrated that the number of lesions promoted in different genes depends on the genotoxic agent and not on their location on a particular domain. Immunodetection of 8-OHdG after H2O2 treatment confirmed that oxidative lesions did not colocalize with histone 3 neither with type IIα + β topoisomerase, but matched perfectly with peroxiredoxin 6, involved in H2O2 metabolism. Results reveal that the head architecture, driving the access of the genotoxicants, highly contributes to the differential susceptibility of nuclear areas, the chromatin packaging playing a minor role. Please refer to pages 401–408 for details.

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