Postreplicative repair is an integral component of lagging strand DNA replication and a suppressor of replication stress

Abstract

Cell division is a basic requirement for the propagation of all organisms. This process begins with a parental cell which divides, leaving two daughter cells. Prior to division, it is necessary for the parental cell to generate a precise duplicate of its genetic material via the process of DNA replication, so that each resulting daughter segregates with a full genetic complement. Errors that occur during this process are thus inherited as mutations by the daughter cells and perpetuated in each subsequent generation along that lineage. Because an estimated 10,000 trillion cell divisions occur in the average lifetime of a human being, it is imperative that this process occurs with a minimum of errors [Quammen 2008]. In the event of difficulty or error, a network of repair and checkpoint pathways has arisen to facilitate the completion of replication with a minimum of inherited mutations [Myung et al. 2001]. The high level of conservation in these replication, repair and checkpoint pathways has allowed us to utilize relatively simple model organisms, such as S. cerevisiae (budding yeast), to better understand how these processes are carried out in more complex metazoan systems. My research has focused on one such group of pathways collectively referred to as postreplicative repair or “PRR” [Chen et al. 2011]. PRR is activated in response to a variety of stressors, which cause difficulty for the replication program and mitigates their impact on genome integrity. The findings included in this dissertation expand our knowledge of stressors, which impact the usage of PRR pathways and moreover describe PRR as an integral component of lagging strand DNA replication.