Byrd Alicia K, Raney Kevin D
Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A.
Biochem Soc Trans. 2017 Oct 15;45(5):1159-1171. doi: 10.1042/BST20170096. Epub 2017 Sep 12.
Pif1 family helicases have multiple roles in the maintenance of nuclear and mitochondrial DNA in eukaryotes. Pif1 is involved in replication through barriers to replication, such as G-quadruplexes and protein blocks, and reduces genetic instability at these sites. Another Pif1 family helicase in , Rrm3, assists in fork progression through replication fork barriers at the rDNA locus and tRNA genes. ScPif1 ( Pif1) also negatively regulates telomerase, facilitates Okazaki fragment processing, and acts with polymerase δ in break-induced repair. Recent crystal structures of bacterial Pif1 helicases and the helicase domain of human PIF1 combined with several biochemical and biological studies on the activities of Pif1 helicases have increased our understanding of the function of these proteins. This review article focuses on these structures and the mechanism(s) proposed for Pif1's various activities on DNA.
Pif1家族解旋酶在真核生物的核DNA和线粒体DNA维持中具有多种作用。Pif1参与通过复制障碍(如G-四链体和蛋白质阻断)进行的复制,并降低这些位点的遗传不稳定性。酿酒酵母中的另一种Pif1家族解旋酶Rrm3,协助复制叉通过rDNA基因座和tRNA基因处的复制叉障碍。酿酒酵母Pif1(ScPif1)也对端粒酶起负调控作用,促进冈崎片段加工,并在断裂诱导修复中与聚合酶δ协同作用。细菌Pif1解旋酶的最新晶体结构以及人类PIF1的解旋酶结构域,结合对Pif1解旋酶活性的多项生化和生物学研究,增进了我们对这些蛋白质功能的理解。这篇综述文章聚焦于这些结构以及针对Pif1在DNA上各种活性所提出的机制。