Premium
Interstitial telomeric DNA sequences of Chinese hamster cells are hypersensitive to nitric oxide damage, and DNA‐PKcs has a specific local role in its repair
Author(s) -
Mosquera Alejandro,
Gosálvez Jaime,
Sabatier Laure,
Fernández José Luis
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20221
Subject(s) - dna damage , dna , microbiology and biotechnology , biology , dna repair , genome instability , genome , genetics , chemistry , gene
The DNA breakage detection–fluorescence in situ hybridization (DBD‐FISH) procedure was used to analyze DNA single‐strand breaks (SSBs) and alkali‐labile sites induced by exposure to the nitric oxide (NO) donors sodium nitroprusside (SNP) and 3‐morpholinosydnomine hydrochloride (SIN‐1) in the whole genome and in long interstitial telomeric repeat sequence (ITRS) blocks from Chinese hamster cells. The relative density of DNA damage generated in the ITRS by X‐rays was similar to that induced in the genome overall, whereas it was 1.7 times higher when the alkylating agent MNNG was assayed. Nevertheless, after SNP or SIN‐1 treatment, ITRSs proved to be 2.8 and 2.7 times relatively more damaged, respectively, than the whole genome. When the DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) was not active, as in XR‐C1 mutant cells, the repair kinetics in the whole genome did not differ from that in the parental cell line with X‐ray or SNP exposure. However, whereas the SSBs and alkali‐labile sites induced in the ITRS by X‐rays exhibited rejoining kinetics similar to that of the parental cell line, the damage induced by SNP was more slowly rejoined. This implies a role for DNA‐PKcs in the repair of DNA damage induced by NO, especially in ITRSs. The results demonstrated intragenomic heterogeneity of NO‐induced DNA damage and repair; there was a higher density of DNA damage in the ITRS blocks, possibly because of their guanine richness. This suggests that a parallel process may occur in the terminal telomeres, which has implications for premature aging and neoplastic development by chronic NO exposure in vivo. © 2005 Wiley‐Liss, Inc.