DNA Damage Signaling Orchestrates SV40 Chromatin Replication

Abstract

The effects of DNA damage signaling on the DNA replication of the polyomavirus SV40 are examined in this dissertation. Infection of monkey cells with SV40 results in large amounts of cellular DNA damage signaling through the cellular kinases ataxia telangiectasia-mutated (ATM) and ATM and Rad3-related (ATR). Literature pertaining to DNA replication, DNA repair, DNA damage signaling, and polyomaviral replication is first discussed. This is followed by a number of experiments testing the molecular mechanisms that necessitate DNA damage signaling by ATM and ATR during SV40 infection. Furthermore, the contribution of ATM and ATR to SV40-induced cell cycle arrest and repair protein recruitment to viral DNA replication centers is explored. After an examination of how my experiments fit in with relevant manuscripts, I discuss the possible consequences of the aberrant products found upon inhibition of DNA damage signaling during SV40 DNA replication and how my current studies can be advanced. Additionally, the connection between DNA damage signaling and DNA repair and the implications of my dissertation to cellular DNA replication are discussed.