CHROMOSOMES WITH HIGH GENE DENSITY ARE PREFERENTIALLY REPAIRED IN HUMAN-CELLS

It is known that DNA repair is heterogeneous in human cells since open chromatin, active genes and their transcribed strands are preferentia lly repaired, It is thus expected that DNA repair is clustered in chro mosomes with high gene density, We have employed a DNA repair inhibito r, cytosine arabinoside (Ara-C), to convert ethyl methane sulfonate (E MS)-induced excision repairable lesions to chromosomal breaks, to chec k for the existence of heterogeneity of repair at the chromosome level , Chromosome staining by fluorescence in situ hybridization (FISH) was used to analyze breakage in chromosomes with diverse gene densities, These chromosomes were identified by means of the CpG island distribut ion after FISH with a CpG island-rich probe isolated from total human genomic DNA. Thus, three chromosomes with very high gene density (numb ers 1, 19 and 20) were compared with two chromosomes with very low gen e density (numbers 4 and 18) for clastogenicity and sensitivity to co- treatment with Ara-C and EMS. Our data indicate that those chromosome with higher gene density are more sensitive to a combination treatment with Ara-C and EMS, indicating that the level of excision repair synt hesis is higher in those chromosome. It is therefore concluded that DN A excision repair is preferentially directed to chromosomes with high gene density. The implications of this finding in human biomonitoring using FISH techniques are discussed.