Preferential localization of γH2AX foci in euchromatin of retina rod cells after DNA damage induction.

Autor: Lafon-Hughes L; Departamento de Genética, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay, llafon@iibce.edu.uy., Di Tomaso MV, Liddle P, Toledo A, Reyes-Ábalos AL, Folle GA
Jazyk: angličtina
Zdroj: Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology [Chromosome Res] 2013 Dec; Vol. 21 (8), pp. 789-803. Date of Electronic Publication: 2013 Dec 10.
DOI: 10.1007/s10577-013-9395-3
Abstrakt: 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.
Databáze: MEDLINE
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