Pif1 family helicases suppress genome instability at G-quadruplex motifs.

Paeschke K, Bochman ML, Garcia PD, Cejka P, Friedman KL, Kowalczykowski SC, Zakian VA
Nature. 2013 497 (7450): 458-62

PMID: 23657261 · PMCID: PMC3680789 · DOI:10.1038/nature12149

The Saccharomyces cerevisiae Pif1 helicase is the prototypical member of the Pif1 DNA helicase family, which is conserved from bacteria to humans. Here we show that exceptionally potent G-quadruplex unwinding is conserved among Pif1 helicases. Moreover, Pif1 helicases from organisms separated by more than 3 billion years of evolution suppressed DNA damage at G-quadruplex motifs in yeast. The G-quadruplex-induced damage generated in the absence of Pif1 helicases led to new genetic and epigenetic changes. Furthermore, when expressed in yeast, human PIF1 suppressed both G-quadruplex-associated DNA damage and telomere lengthening.

MeSH Terms (16)

Base Sequence Conserved Sequence DNA Damage DNA Helicases Epigenesis, Genetic Evolution, Molecular G-Quadruplexes Gene Silencing Genetic Complementation Test Genomic Instability Humans Molecular Sequence Data Mutation Rate Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Telomere Homeostasis

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