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Pif1 helicases: helping replication forks maneuver past replication barriers
Author(s) -
Bochman Matthew L.,
Paeschke Katrin,
Garcia Patricia,
Zakian Virginia A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.95.1
Subject(s) - helicase , telomere , biology , telomerase , genetics , dna replication , microbiology and biotechnology , dna , gene , rna
Pif1 family 5′ to 3′ DNA helicases are found in all three domains of life. Mutation of the human PIF1 is correlated with increased propensity to breast cancer. The best studied Pif1 helicase is the multifunctional S. cerevisiae Pif1 (ScPif1). Published work shows that ScPif1 has key roles in maintenance of mitochondrial DNA, limiting telomerase processivity, processing Okazaki fragments, and suppressing DNA damage at G‐quadruplex (G4) motifs. Here we report in vitro studies that demonstrate that the budding yeast Pif1 and five bacterial Pif1 helicases are extremely proficient at unfolding G4 structures, able to do so even under single cycle conditions. In addition, ScPif1 appears to load onto G4 substrates by interacting with the G‐stacks in the G4 structure rather than the single strand loops. We used the gross chromosomal rearrangement (GCR) assay to determine if Pif1 helicases suppress DNA damage at G4 motifs. The two budding yeast Pif1 proteins, ScPif1 and ScRrm3, four bacterial Pif1 helicases, and fission yeast and human PIF1 are highly effective suppressors of G4‐induced DNA damage. The survivors of G4‐induced instability in Pif1 deficient cells have an unprecedented post‐GCR structure that involves mutation of the G4 motif and stable silencing of the marker genes used in the assay. Like ScPif1, human PIF1 (but not S. pombe or bacterial Pif1 helicases) represses telomere lengthening in S. cerevisiae .