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Title [sv]
Det essentiella helikaset Pfh1s roll i arvsmassans integritet
Title [en]
Function of the essential Pfh1 helicase in genome integrity
Abstract [sv]
The goal of this work is to contribute to our understanding of the mechanisms that promote genome integrity by studying S. pombe (fission yeast) Pif1 helicase, Pfh1. Pfh1 belongs to an evolutionary conserved 5´-3´ helicase family and is essential for both nuclear and mitochondrial genome maintenance. During DNA synthesis, the replisome encounters impediments, such as stable protein-DNA complexes. These natural impediments slow fork movement which may cause DNA breakage. Pfh1 possesses the unique ability to promote fork progression through these natural impediments, including highly transcribed RNA Polymerase II and III genes. It is not understood how Pfh1 promotes fork progression at these sites in order to coordinate DNA synthesis with other mechanisms that compete with the fork for the same DNA substrate, such as transcription and co-transcriptional processes. My research will focus on determining the function of Pfh1 in both nuclear and mitochondrial replication progression by combining biochemical and genetic assays, as well as genome-wide methods, such as ChIP-seq. Increased knowledge about the function of Pif1 families is extremely relevant to human health, as a mutation in the human homolog, hPIF, has been identified in several families with a high incidence of breast cancer. The corresponding human mutation in Pfh1 cannot supplement its essential functions in S. pombe, suggesting our proposed studies in yeast will serve as a good model for the more complex human cell.
Principal InvestigatorSabouri, Nasim
Coordinating organisation
Umeå University
Funder
Period
2013-01-01 - 2016-12-31
National Category
Biochemistry and Molecular BiologyCell Biology
Identifiers
DiVA, id: project:1211Project, id: 2012-03087_VR

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