Role of Lamin A and Telomerase in DNA Damage Response

Abstract

Lamins are intermediate filament proteins that maintain structural and mechanical integrity of the nucleus. Lamins are important in maintenance of the epigenetic landscape, DNA replication and mechanotransduction. Lamins have also been implicated in DNA damage response. Telomerase – a reverse transcriptase enzyme expressed in germ cells and deregulated in cancers, protects transformed cells against DNA damage. In this study, we attempted to understand the coregulatory role of Lamin A and Telomerase in DNA Damage response. Down regulation of Lamin A using shRNA in HT1080 (Telomerase positive) and U2OS (Telomerase negative) cells led to significant decrease in 53BP1 (a key regulator of NHEJ mediated DNA damage repair pathway) foci volumes and changes in foci numbers upon DNA damage induction using Cisplatin. Lamin A downregulated cells showed an enrichment of the 53BP1 foci at the nuclear periphery. HT1080 cells stably overexpressing Telomerase showed comparable levels of basal DNA damage despite being aneuploid and displayed significant downregulation of B-type Lamins. This data suggests a potential cross talk between Telomerase and Lamins in regulating DNA damage response.