Chromatin remodelling and chromosome damage distribution.
Histone acetylation/deacetylation constitute the most relevant chromatin remodelling mechanism to control DNA access to nuclear machinery as well as to mutagenic agents. Thus, these epigenetics mechanisms could be involved in processing DNA lesions into chromosomal aberrations. Although radiation-induced DNA lesions are believed to occur randomly, in most cases chromosome breakpoints appear distributed in a non-random manner. In order to study the distribution of chromosome damage induced by clastogenic agents in relation to chromosome histone acetylation patterns, an experimental model based on treating Chinese hamster cells with endonucleases and ionizing radiations as well as immunolabelling metaphase chromosomes with antibodies to acetylated histone H4 was developed. The analysis of intra- and interchromosome breakpoint distribution has been carried out on G-banded chromosomes, and results obtained were correlated with chromosome acetylated histone H4 profiles. A co-localization of intrachromosomal breakpoints induced by Alu I, Barn HI and DNase I as well as by neutrons and gamma-rays was observed. Radiation- and endonuclease-induced breakpoints tend to cluster in less condensed chromosome regions (G-light bands) that show the highest levels of acetylated histone H4. The analysis of interchromosomal distribution of radiation-induced lesions showed a concentration ofbreakpoints in Chinese hamster chromosomes with particular histone acetylation patterns. The fact that chromosome break-points occur more frequently in transcriptionally competent chromosome regions suggests that chromatin conformation and nuclear architecture could play a role in the distribution of chromosome lesions.
Martínez-López
W
W
Department of Genetic Toxicology and Chromosome Pathology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. wlopez@iibce.edu.uy
Di Tomaso
M V
MV
D000107:Acetylation; D000818:Animals; D016466:CHO Cells; D042002:Chromatin Assembly and Disassembly / Q000502:physiology* / Q000528:radiation effects; D002871:Chromosome Banding; D019457:Chromosome Breakage / Q000502:physiology*; D006224:Cricetinae; D020732:Cytogenetic Analysis; D004720:Endonucleases / Q000378:metabolism; D006657:Histones / Q000378:metabolism* / Q000528:radiation effects; D011839:Radiation, Ionizing
D006657:Histones; D004720:Endonucleases