Preferential localization of γh2AX foci in euchromatin of retina rod cells after DNA damage induction
Chromosome Res. 2013-12-01; 21(8): 789-803
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1. Chromosome Res. 2013 Dec;21(8):789-803. doi: 10.1007/s10577-013-9395-3. Epub 2013
Preferential localization of γH2AX foci in euchromatin of retina rod cells after
DNA damage induction.
Lafon-Hughes L(1), Di Tomaso MV, Liddle P, Toledo A, Reyes-Ábalos AL, Folle GA.
(1)Departamento de Genética, Instituto de Investigaciones Biológicas Clemente
Estable, Montevideo, Uruguay, .
DNA damage may lead to cell transformation, senescence, or death. Histone H2AX
phosphorylation, immunodetected as γH2AX foci, is an early response to DNA damage
persisting even after DNA repair. In cycling mammalian cells with canonical
nuclear architecture, i.e., central euchromatin and peripheral heterochromatin,
γH2AX foci map preferentially to euchromatin. Mice retina rods are G0 cells
displaying an inverted nuclear architecture 28 days after birth (P28). Rod nuclei
exhibit one or two central constitutive heterochromatin chromocenters encircled
by facultative heterochromatin. Euchromatin resides at the nuclear periphery,
extending to the equator in cells with two chromocenters. To assess the impact of
chromatin relocation in the localization of DNA damage, γH2AX and TUNEL foci
induced ex vivo by radiomimetic bleomycin were mapped in H3K4me3 immunolabeled
P28 rod nuclei. A preferential localization of γH2AX foci in euchromatin was
detected together with foci clustering. Besides, a decay of H3K4me3 signal at
γH2AX foci sites was observed. TUNEL and γH2AX foci exhibited similar
localization patterns in BLM-treated rod cells thus excluding curtailed access of
anti-γH2AX antibodies to heterochromatin. Lack of γH2AX foci in rod chromocenters
appears to be unrelated to the occurrence of mid-range foci movements. Foci
clusters may arise through DNA double-strand break proximity, local
non-directional chromatin movements or chromatin relaxation. H3K4me3 signal
reduction at γH2AX foci could stem from local chromatin decondensation or
downregulation of histone H4 methylation. The observed topology of DNA damage in
retina-differentiated rods indicates that euchromatin is damage-prone, regardless
of the canonical or inverted nuclear architecture of mammalian cells.
PMID: 24323064 [Indexed for MEDLINE]