Roles of Pif1-like helicases in the maintenance of genomic stability.

Roles of Pif1-like helicases in the maintenance of genomic stability.
复制标题

PIF1样解旋酶在维持基因组稳定性中的作用。

DOI:
10.1093/nar/gkl561
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发表时间:
2006
影响因子:
14.9
通讯作者:
Zakian VA
Zakian VA
中科院分区:
生物学2区
文献类型:
--
作者:
Boulé JB;Zakian VA

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DNA解旋酶的Pif 1 p家族从酵母到人类都是保守的。到目前为止,这个家庭的四个成员已经在一些详细的体外和体内分析:两个面包酵母解旋酶,ScPif 1 p和Rrm 3 p,裂殖酵母Pfh 1 p和人类酶hPif 1 p。在体外,这些酶是5′至3′ DNA解旋酶,并表现出很小的持续合成能力。在体内,ScPif 1 p,Rrm 3 p和可能Pfh 1 p,在细胞核中的特定基因组位点和线粒体中发挥作用,在线粒体中,它们作为复制机制的辅助解旋酶被需要用于基因组的稳定维持。有趣的是,它们作用于常见的DNA底物,但似乎具有很大程度上不重叠的细胞功能,从冈崎片段加工,端粒酶抑制,到帮助复制叉通过非核小体蛋白-DNA复合物。例如,ScPif 1 p和Rrm 3 p都影响端粒的复制,但方式不同:Pif 1 p通过直接从DNA末端去除端粒酶来抑制端粒酶介导的端粒延伸,而Rrm 3 p通过端粒DNA促进复制。在这里,我们回顾了目前的知识PIF 1样解旋酶,作为第一步了解其功能的专业化和作用机制的基础。
The Pif1p family of DNA helicases is conserved from yeast to humans. To date, four members of this family have been analyzed in some detail by in vitro and in vivo assays: the two baker's yeast helicases, ScPif1p and Rrm3p, the fission yeast Pfh1p and the human enzyme hPif1p. In vitro, these enzymes are 5′ to 3′ DNA helicase and show little processivity. In vivo, ScPif1p, Rrm3p and probably Pfh1p, function in both the nucleus at specific genomic loci and in mitochondria, where they are needed for the stable maintenance of the genome as accessory helicases to the replication machinery. Interestingly, they act on common DNA substrates but appear to have largely non-overlapping cellular functions, ranging from Okazaki fragment processing, telomerase inhibition, to helping the replication fork progress through non-nucleosomal protein–DNA complexes. For example, both ScPif1p and Rrm3p affect the replication of telomeres, but in a different way: Pif1p inhibits telomerase-mediated telomere elongation by directly removing telomerase from a DNA end, whereas Rrm3p facilitates replication through telomeric DNA. Here we review the current knowledge on the Pif1-like helicases, as a first step towards understanding the basis of their functional specialization and mechanism of action.
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