DNA response to bleomycin in mammalian cells with variable degrees of chromatin condensation

Abstract

BLM induces DNA degradation in living cells. We used CHO cells with maximal chromatin compactness (cells synchronized in metaphase), cells with chromatin decondensed by Na butyrate treatments, and control cells with normal chromatin condensation in order to analyse the correlation between chromatin compactness, DNA sensitivity to BLM, efficiency of repair of BLM-induced DNA lesions, and cell viability. We found that the DNA sensitivity to BLM and the efficiency of DNA repair is inversely correlated with the degree of chromatin coiling. Cells with decondensed chromatin are those showing higher DNA sensitivity to BLM but also those having the best efficiency to mend the damage. Accordingly, these cells show an amount of residual DNA lesions and a curve of growth similar to that of control cells. The situation is just the opposite for metaphase cells. The DNA of these cells is more resistant to BLM, but the damage is poorly repaired. The final result is that BLM induces a higher concentration of residual DNA lesions and a lower viability in metaphase than in control cells. Our results suggest that chromatin structure influences the quantity and reparability of the BLM-induced lesions, producing a higher incidence of double strand break in the DNA of cells with marked chromatin condensation.

A comparative analysis of bleomycin‐induced incomplete chromosome elements in two mammalian cell lines using a telomeric PNA probe

“…DOI 10.1002/em derived cells, confirming that the chromosomes of mammalian cells exhibit differential sensitivity to BLM [Povirk and Austin, 1991]. Although further studies are needed to determine the reason for this difference, a lower level of BLM-induced DNA damage, a greater repair efficiency, and perhaps more efficient BLM hydrolases could be factors explaining why CPC cells are less sensitive than CHE cells to BLM-induced chromosomal damage López-Larraza and Bianchi, 1993;Galm et al, 2005]. ( In spite of the differential chromosomal sensitivity to BLM exhibited by CHE and CPC cells, both cell lines showed induction of ICE.…”

“…The fact that chromosomal incompleteness is much more frequent in BLM-treated cells than in ionizing radiation-exposed cells could be due to the complexity of the DNA damage after BLM treatment, since, unlike ionizing radiation, this antibiotic intercalates in the DNA inducing single-and double-strand breaks. The sensitivity of DNA to BLM and the efficiency of the repair of DNA lesions induced by this compound are modulated by several factors, including the base composition [Takeshita et al, 1978], the chromatin structure [Vig and Lewis, 1978;Bianchi et al, 1990;López-Larraza et al, 1990;López-Larraza and Bianchi, 1993], and the activity of BLM-hydrolase [Chen and Stubbe, 2005;Galm et al, 2005].…”

Molecular Association between ATR and Two Components of the Nucleosome Remodeling and Deacetylating Complex, HDAC2 and CHD4

“…One model is that CHD4's presence in the complex indicates that ATR is associated with heterochromatin. Early work on DNA damage focused on how repair could occur in DNA condensed in nucleosomes and some studies indicate that repair enzymes have difficulty accessing condensed DNA ( , ). In this model, ATR could be the guardian of heterochromatin, sampling DNA to check for damage in densely compacted DNA by unfolding and refolding heterochromatin.…”

Chromosomal response of insect and mammalian cells to streptonigrin: A comparative study

“…There is abundant information indicating that the chromosomal sensitivity of mammalian cells to clastogenic compounds is closely related with the chromatin fibril structure [Kuo and Hsu, 1979;Kuo, 1981;López-Larraza and Bianchi, 1993;Smith et al, 1986]. Recently, we analyzed the sensitivity to SN of CHO chromosomes substituted with different halogenated compounds and found that DNA substitution with BrdUrd or IdUrd potentiates the chromosome damage induced by the antibiotic.…”