Genetic Interactions Implicating Postreplicative Repair in Okazaki Fragment Processing

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Genome duplication via the process of DNA replication is a prerequisite for cell division and underlies the propagation of all living organisms. This fundamentally important mechanism has been highly conserved throughout eukaryotic evolution, allowing us to use the relatively simple and genetically tractable Saccharomyces cerevisiae as a model to better understand DNA replication in human cells. Furthermore, there is strong evidence to suggest that defects in DNA replication are prominent contributors to mutation and genome instability, a hallmark of cancer. Not surprisingly, evolution has selected for mechanisms to mitigate the effects of defective replication and avoid the most harmful outcomes. Postreplicative repair (PRR) pathways are two such mechanisms with well described functions in promoting the completion of replication under adverse conditions. In this study, we utilized a non-biased genome wide genetic screen to systematically identify conditions under which PRR is required. Our findings indicate that in addition to previously described roles in rescuing DNA synthesis defects, PRR is also required in response to aberrant DNA processing. Specifically, we report a requirement for PRR in cells lacking RAD27, the yeast homolog of the tumor suppressor FEN1. These findings expand the known functions of PRR and reveal their importance in promoting the viability of cells lacking a known tumor suppressor.

Vyšlo v časopise: Genetic Interactions Implicating Postreplicative Repair in Okazaki Fragment Processing. PLoS Genet 11(11): e32767. doi:10.1371/journal.pgen.1005659
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005659

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