Effect of Ataxia-Telangiectasia Mutated (ATM) and cell cycle stage on telomere overhang maintenance

Bhusari, Amruta
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Telomeres, the physical ends of chromosomes, are indispensable for maintaining genomic stability. Telomeres end in 3&feet; single stranded G-overhangs. The 3&feet; overhang is a site where telomerase binds and extends short telomeres. The overhang also participates in the formation of t-loop that protects telomere ends from being recognized as damaged sites. Thus, studying the maintenance of telomere overhangs has become an important aspect of telomere biology. The Ataxia-Telangiectasia Mutated (ATM) protein, encoded by the ATM gene, belongs to the phosphatidyl inositol 3-kinase (PI3K) like kinase (PI3KK) family of proteins. It plays a major role in DNA damage repair and cell cycle regulation. The function of ATM at human telomeres is unclear. In this study, the effect of ATM kinase inhibition on the telomere G-overhang and also the regulation of telomere overhang were studied. This enabled us to understand the particular phase in which the overhang is generated. By telomere overhang protection assay I found that ATM kinase inhibition does not have any effect on the size of telomere overhang length. Also, the generation of telomere overhang is cell cycle stage specific and is independent of telomerase activity. Understanding the mechanism of G-overhang generation in human cells will ultimately help in finding solutions to curb premature aging and cancer.

Biological sciences, Cellular biology, Molecular biology