The Pif1 family helicase Pfh1 facilitates telomere replication and has an RPA-dependent role during telomere lengthening

McDonald, Karin R.; Sabouri, Nasim; Webb, Christopher J.; Zakian, Virginia A.

doi:10.1016/j.dnarep.2014.09.008

Cited by 32 publications

(38 citation statements)

References 37 publications

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“…Noteworthy, a milder overexpression of Pfh1 Pif1 with pREP41 did not restore telomere length of D223Y cells (Supplementary Fig S6). Consistent with a recent study, we observed that overexpression of Pfh1 Pif1 by itself slightly lengthened the telomeres of a WT strain (Fig A, lanes 6, 7) (McDonald et al , ). Thus, among the tested helicases, only Pfh1 Pif1 was able to rescue the telomere defect of the D223Y mutant.…”

Section: Resultssupporting

confidence: 92%

RPA prevents G‐rich structure formation at lagging‐strand telomeres to allow maintenance of chromosome ends

et al. 2015

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Replication protein A (RPA) is a highly conserved heterotrimeric single-stranded DNA-binding protein involved in DNA replication, recombination, and repair. In fission yeast, the Rpa1-D223Y mutation provokes telomere shortening. Here, we show that this mutation impairs lagging-strand telomere replication and leads to the accumulation of secondary structures and recruitment of the homologous recombination factor Rad52. The presence of these secondary DNA structures correlates with reduced association of shelterin subunits Pot1 and Ccq1 at telomeres. Strikingly, heterologous expression of the budding yeast Pif1 known to efficiently unwind G-quadruplex rescues all the telomeric defects of the D223Y cells. Furthermore, in vitro data show that the identical D to Y mutation in human RPA specifically affects its ability to bind G-quadruplex. We propose that RPA prevents the formation of G-quadruplex structures at lagging-strand telomeres to promote shelterin association and facilitate telomerase action at telomeres.

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Section: Resultssupporting

confidence: 92%

RPA prevents G‐rich structure formation at lagging‐strand telomeres to allow maintenance of chromosome ends

et al. 2015

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“…However, pfh1Δ spore clones, which divide only a few times before they arrest in G2 phase, have modestly shorter telomeres than wild type cells [53]. Moreover, over-expressing Pfh1 increases telomere length by a recombination-independent mechanism, and this lengthening does not occur in rad11-D223Y cells [54], in which telomerase action is inefficient [55]. As Pfh1 promotes telomere lengthening in a telomerase-dependent manner, it is unlikely to be an inhibitor of telomerase.…”

Section: Pif1 Family Helicases Affect Telomerasementioning

confidence: 99%

“…By both 2D gels and ChIP experiments, depleting cells of Pfh1 slows fork progression within telomeres [11,54]. …”

Section: Rrm3 and Pfh1 Helicases Promote Semi-conservative Replicamentioning

confidence: 99%

“…If telomeric G-tails fold into an intra-molecular G4 structure, ScPif1 could unwind it, but this unwinding is unlikely to explain ScPif1’s inhibition of telomerase as intra-molecular G4 structures inhibit telomerase [77,78] (although it could explain how Pfh1 promotes fission yeast telomerase [54,79]). A more appealing model is that ScPif1 removes telomerase from DNA ends by unwinding the RNA/DNA hybrid that forms between the template region in telomerase RNA and the single-stranded G-tail (Fig.…”

Section: Biochemical Functions Of Pif1 Family Helicases Provide Himentioning

confidence: 99%

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Getting it done at the ends: Pif1 family DNA helicases and telomeres

Geronimo

Zakian

2016

DNA Repair

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It is widely appreciated that the ends of linear DNA molecules cannot be fully replicated by the conventional replication apparatus. Less well known is that semi-conservative replication of telomeric DNA also presents problems for DNA replication. These problems likely arise from the atypical chromatin structure of telomeres, the GC-richness of telomeric DNA that makes it prone to forming DNA secondary structures, and from RNA-DNA hybrids, formed by transcripts of one or both DNA strands. Given the different aspects of telomeres that complicate their replication, it is not surprising that multiple DNA helicases promote replication of telomeric DNA. This review focuses on one such class of DNA helicases, the Pif1 family of 5′–3′ DNA helicases. In budding and fission yeasts, Pif1 family helicases impact both telomerase-mediated and semi-conservative replication of telomeric DNA as well as recombination-mediated telomere lengthening.

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“…Similar to ScPif1, S. pombe Pfh1 (PIF1-homolog-1) maintains mtDNA integrity. In addition, both ScPIF1 and SpPfh1 maintain telomeric DNA integrity and normal telomere length (SCHULZ AND ZAKIAN 1994;MCDONALD et al 2014). However, loss of Pfh1 is lethal (ZHOU et al 2002;PINTER et al 2008), while deletion of S. cerevisiae Pif1 is not, for reasons that are still not understood.…”

Section: Introductionmentioning

confidence: 99%

TheDrosophila melanogasterPIF1 helicase promotes survival during replication stress and processive DNA synthesis during double-strand gap repair

Kocak

Dykstra

Németh

et al. 2019

Preprint

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PIF1 is a 5' to 3' DNA helicase that can unwind double-stranded DNA and disrupt nucleic acidprotein complexes. In Saccharomyces cerevisiae, Pif1 plays important roles in mitochondrial and nuclear genome maintenance, telomere length regulation, unwinding of G-quadruplex structures, and DNA synthesis during break-induced replication. Some, but not all, of these functions are shared with other eukaryotes. To gain insight into the evolutionarily conserved functions of PIF1, we created pif1 null mutants in Drosophila melanogaster and assessed their phenotypes throughout development. We found that pif1 mutant larvae exposed to high concentrations of hydroxyurea, but not other DNA damaging agents, experience reduced survival to adulthood.Embryos lacking PIF1 fail to segregate their chromosomes efficiently during early nuclear divisions, consistent with a defect in DNA replication. Furthermore, loss of the BRCA2 protein, which is required for homologous recombination and stabilization of stalled replication forks in metazoans, causes synthetic lethality in third instar larvae lacking either PIF1 or the polymerase delta subunit POL32. Interestingly, pif1 mutants have a reduced ability to synthesize DNA during repair of a double-stranded gap, but only in the absence of POL32. Together, these results support a model in which Drosophila PIF1 functions to promote efficient DNA synthesis during times of replication stress and acts independently of POL32 to promote synthesis during doublestrand gap repair.

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The Pif1 family helicase Pfh1 facilitates telomere replication and has an RPA-dependent role during telomere lengthening

Cited by 32 publications

References 37 publications

RPA prevents G‐rich structure formation at lagging‐strand telomeres to allow maintenance of chromosome ends

RPA prevents G‐rich structure formation at lagging‐strand telomeres to allow maintenance of chromosome ends

Getting it done at the ends: Pif1 family DNA helicases and telomeres

TheDrosophila melanogasterPIF1 helicase promotes survival during replication stress and processive DNA synthesis during double-strand gap repair

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