Localized DNA cleavage secondary to genotoxic exposure adjacent to an Alu inverted repeat

Genes, Chromosomes & Cancer
Bay HoAndrew T Vaughan

Abstract

Radiation is a potent inducer of DNA damage leading to both random DNA loss and mutation. As part of a study focused on the mechanism whereby cells undergo loss of heterozygosity (LOH), a region of common LOH telomeric termination at 11q24 was observed in clones of H292 mucoepidermoid cells established after irradiation (IR). A 10-kbp region including the telomeric extent of LOH termination was analyzed after IR using six sets of ligation-mediated polymerase chain reaction (PCR) primers to detect the presence of DNA breaks. A cluster of DNA breaks was detected that closely mapped to the telomeric extent of LOH and which were observed up to 8 hr after IR. Repeating the experiment in the presence of the inhibitor of apoptosis, zVAD.fmk, did not change the location or amount of cleavage. A similar distribution of breaks was also seen in the MCF-10A breast cancer cell line after IR. Further inspection of the involved region showed that 22/32 and 7/7 DNA breaks found in H292 and MCF-10A cells, respectively, were located either in or immediately adjacent to an AluSx1 sequence, itself ≈ 1 kbp 5' to an AluSq2 that was in an inverted orientation to the AluSx1. The region between the inverted Alu repeats was notable for both DNAse hypers...Continue Reading

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Jun 18, 2015·Cellular and Molecular Life Sciences : CMLS·Maria SuntsovaAnton Buzdin
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