gammaH2AX signalling during sperm chromatin remodelling in the mouse zygote.
In the mouse, the paternal post-meiotic chromatin is assumed to be devoid of DNA repair after nuclear elongation and protamine-induced compaction. Hence, DNA lesions induced thereafter will have to be restored upon gamete fusion in the zygote. Misrepair of such lesions often results in chromosome type aberrations at the first cleavage division, suggesting that the repair event takes place prior to S-phase. During this stage of the zygotic cell cycle, the paternal chromatin transits from a protamine- to a nucleosome-based state. We addressed the question whether the canonical signalling pathway to DNA double strand breaks (DSBs), the phosphorylated form of histone H2AX (gammaH2AX) is active during chromatin restructuring of the male genetic complement in the zygote. Here, we describe the detailed characterization of gammaH2AX signalling in the early stages of zygotic development up to the appearance of the pronuclei. We have found the gammaH2AX signalling pathway to be already active during sperm chromatin remodelling after gamete fusion in a dose dependent manner, reflecting the amount of DSBs present in the sperm nucleus after in vivo male irradiation. Using DNA damaging compounds to induce lesions in the early zygote, differences in DSB sensitivity and gammaH2AX processing between paternal and maternal chromatin were found, suggesting differences in DNA repair capacity between the parental chromatin sets.
Derijck
Alwin A H A
AA
Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
van der Heijden
Godfried W
GW
Giele
Maud
M
Philippens
Marielle E P
ME
van Bavel
Casandra C A W
CC
de Boer
Peter
P
D000818:Animals; D001761:Bleomycin; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D005047:Etoposide; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D012737:Sex Factors; D015398:Signal Transduction / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology*; D015053:Zygote / Q000166:cytology / Q000378:metabolism*
D001761:Bleomycin; D005047:Etoposide; D006657:Histones; C475961:gamma-H2AX protein, mouse