Abstract
The two PIF1 family helicases in Saccharomyces cerevisiae, Rrm3, and ScPif1, associate with thousands of sites throughout the genome where they perform overlapping and distinct roles in telomere length maintenance, replication through non-histone proteins and G4 structures, lagging strand replication, replication fork convergence, the repair of DNA double-strand break ends, and transposable element mobility. ScPif1 and its fission yeast homolog Pfh1 also localize to mitochondria where they protect mitochondrial genome integrity. In addition to yeast serving as a model system for the rapid functional evaluation of human Pif1 variants, yeast cells lacking Rrm3 have proven useful for elucidating the cellular response to replication fork pausing at endogenous sites. Here, we review the increasingly important cellular functions of the yeast PIF1 helicases in maintaining genome integrity, and highlight recent advances in our understanding of their roles in facilitating fork progression through replisome barriers, their functional interactions with DNA repair, and replication stress response pathways.
Highlights
The two PIF1 family helicases in Saccharomyces cerevisiae, Rrm3, and ScPif1, associate with thousands of sites throughout the genome where they perform overlapping and distinct roles in telomere length maintenance, replication through non-histone proteins and G4 structures, lagging strand replication, replication fork convergence, the repair of DNA double-strand break ends, and transposable element mobility
Though unresolved G4 structures act as barriers to DNA replication and can cause genome instability, sequences capable of adopting G4 structures are enriched at human origins of replication, gene promoters, telomeres, as well as in ribosomal DNA (rDNA) and the mitochondrial genome, suggestive of a functional role
In contrast to rrm3∆-sensitive fragile sites that are caused by impeded replication forks encountering non-nucleosomal DNA-bound proteins, fragile site expression in RSZs is the result of depletion of the dNTP pool [178], suggesting that two types of fragile sites exist within the yeast genome: dNTP-sensitive (RSZ) and rrm3-sensitive
Summary
The PIF1 DNA helicase family is conserved from bacteria to mammals [1,2]. While the yeast. DNA recombination mutation 3 (RRM3) gene was identified and later classified as a member of the PIF1 DNA helicase family based on sequence similarity [4,5]. Both Rrm and ScPif belong to the superfamily 1B and have 50 –30 translocase activity that is encoded in helicase domains that share 40%. N-terminal extensions of Rrm and ScPif to regulate their enzymatic activity and their recruitment to specific sites within the yeast genome, where they perform the many distinct cellular functions discussed in this review
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