TY - JOUR
T1 - DNA Replication through G-Quadruplex Motifs Is Promoted by the Saccharomyces cerevisiae Pif1 DNA Helicase
AU - Paeschke, Katrin
AU - Capra, John A.
AU - Zakian, Virginia A.
N1 - Funding Information:
We thank B.A. Lenzmeier for strains and advice on the recombination assay and C. Webb, N. Sabouri, M. Bochman, and J. Broach for comments on the manuscript. This work was supported by NIH grant GM26938 (V.A.Z.) and postdoctoral fellowships from Deutsche Forschungsgemeinschaft and NJCCR (K.P.).
PY - 2011/5/27
Y1 - 2011/5/27
N2 - G-quadruplex (G4) DNA structures are extremely stable four-stranded secondary structures held together by noncanonical G-G base pairs. Genome-wide chromatin immunoprecipitation was used to determine the in vivo binding sites of the multifunctional Saccharomyces cerevisiae Pif1 DNA helicase, a potent unwinder of G4 structures in vitro. G4 motifs were a significant subset of the high-confidence Pif1-binding sites. Replication slowed in the vicinity of these motifs, and they were prone to breakage in Pif1-deficient cells, whereas non-G4 Pif1-binding sites did not show this behavior. Introducing many copies of G4 motifs caused slow growth in replication-stressed Pif1-deficient cells, which was relieved by spontaneous mutations that eliminated their ability to form G4 structures, bind Pif1, slow DNA replication, and stimulate DNA breakage. These data suggest that G4 structures form in vivo and that they are resolved by Pif1 to prevent replication fork stalling and DNA breakage.
AB - G-quadruplex (G4) DNA structures are extremely stable four-stranded secondary structures held together by noncanonical G-G base pairs. Genome-wide chromatin immunoprecipitation was used to determine the in vivo binding sites of the multifunctional Saccharomyces cerevisiae Pif1 DNA helicase, a potent unwinder of G4 structures in vitro. G4 motifs were a significant subset of the high-confidence Pif1-binding sites. Replication slowed in the vicinity of these motifs, and they were prone to breakage in Pif1-deficient cells, whereas non-G4 Pif1-binding sites did not show this behavior. Introducing many copies of G4 motifs caused slow growth in replication-stressed Pif1-deficient cells, which was relieved by spontaneous mutations that eliminated their ability to form G4 structures, bind Pif1, slow DNA replication, and stimulate DNA breakage. These data suggest that G4 structures form in vivo and that they are resolved by Pif1 to prevent replication fork stalling and DNA breakage.
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U2 - 10.1016/j.cell.2011.04.015
DO - 10.1016/j.cell.2011.04.015
M3 - Article
C2 - 21620135
AN - SCOPUS:79957556530
SN - 0092-8674
VL - 145
SP - 678
EP - 691
JO - Cell
JF - Cell
IS - 5
ER -