Structure and function of Pif1 helicase

Byrd, Alicia K.; Raney, Kevin D.

doi:10.1042/bst20170096

Cited by 56 publications

(55 citation statements)

References 113 publications

(211 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In Pif1 helicases, all conserved helicase motifs, including the SM, are present in domains 1A and 2A ( 40 ). The SM is folded into an α-helix, a loop and part of a β sheet ( 41–43 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Pif1 signature motif of Pfh1 is necessary for both protein displacement and helicase unwinding activities, but is dispensable for strand-annealing activity

Mohammad

Wallgren

Sabouri

2018

Nucleic Acids Research

View full text Add to dashboard Cite

Pfh1, the sole member of the Pif1 helicases in Schizosaccharomyces pombe, is multifunctional and essential for maintenance of both the nuclear and mitochondrial genomes. However, we lack mechanistic insights into the functions of Pfh1 and its different motifs. This paper is specifically concerned with the importance of the Pif1 signature motif (SM), a 23 amino acids motif unique to Pif1 helicases, because a single amino acid substitution in this motif is associated with increased risk of breast cancer in humans and inviability in S. pombe. Here we show that the nuclear isoform of Pfh1 (nPfh1) unwound RNA/DNA hybrids more efficiently than DNA/DNA, suggesting that Pfh1 resolves RNA/DNA structures like R-loops in vivo. In addition, nPfh1 displaced proteins from DNA and possessed strand-annealing activity. The unwinding and protein displacement activities were dependent on the SM because nPfh1 without a large portion of this motif (nPfh1-Δ21) or with the disease/inviability-linked mutation (nPfh1-L430P) lost these properties. Unexpectedly, both nPfh1-L430P and nPfh1-Δ21 still displayed binding to G-quadruplex DNA and demonstrated strand-annealing activity. Misregulated strand annealing and binding of nPfh1-L430P without unwinding are perhaps the reasons that cells expressing this allele are inviable.

show abstract

“…In Pif1 helicases, all conserved helicase motifs, including the SM, are present in domains 1A and 2A ( 40 ). The SM is folded into an α-helix, a loop and part of a β sheet ( 41–43 ).…”

Section: Discussionmentioning

confidence: 99%

“…There are four available crystal structures of Pif1 helicases ( 40 ), including the Bacteroides sp. 2-1-16 Pif1 (BaPif1) ( 41 ), Bacteroides sp.…”

Section: Introductionmentioning

confidence: 99%

The Pif1 signature motif of Pfh1 is necessary for both protein displacement and helicase unwinding activities, but is dispensable for strand-annealing activity

Mohammad

Wallgren

Sabouri

2018

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…SF1B-type helicases are found broadly across all domains of life and include the well-studied pif1 and recD (Saikrishnan et al 2009). In eukaryotes such as Saccharomyces cerevisiae, pif1 has been implicated in telomere maintenance, Okazaki fragment processing, and resolution of G-quadruplex motifs (Byrd & Raney 2017), while recD is a core component of the E. coli RecBCD complex involved in DNA processing and repair (Singleton et al 2004). Another prototypical SF1B-type helicase is dda , encoded by phage T4, which is a non-essential accessory helicase implicated in origin melting, translocating proteins off DNA, and a wide variety of other functions in vitro , although its exact role in vivo is unknown (He et al 2012; Byrd & Raney 2006; Brister 2008).…”

Section: Resultsmentioning

confidence: 99%

“…SF1B-type helicases are implicated in activities ranging from replication and genome maintenance to transcriptional regulation (Byrd & Raney 2017). Additionally, the S. aureus phage parasites, SaPIs, make use of dUTPases as anti-repressors to initiate the transcriptional program of the island, suggesting that these genomic islands can evolve to respond to phage-encoded proteins independent of their biological function for the phage (Tormo-Más et al 2010; Bowring et al 2017).…”

Section: Resultsmentioning

confidence: 99%

Viral satellites exploit phage proteins to escape degradation of the bacterial host chromosome

McKitterick

Hays

Alam

et al. 2019

Preprint

View full text Add to dashboard Cite

SummaryPhage defense systems are often found on mobile genetic elements (MGEs), where they constitutively defend against invaders or are induced to respond to new assaults. Some MGEs, the phage satellites, exploit phages for their own transmission after induction, reducing phage production and protecting their hosts in the process. One such satellite in Vibrio cholerae, PLE, is triggered by the lytic phage ICP1 to excise from the chromosome, replicate, and transduce to neighboring cells, completely sabotaging phage production. Here, we found that ICP1 has evolved to possess one of two syntenic loci encoding an SF1B-type helicase, either of which PLE can exploit to directly drive PLE replication. Further, loss of PLE mobilization limits anti-phage activity due to phage-mediated degradation of the bacterial genome. Our work provides insight into the unique challenges imposed on the parasites of lytic phages and underscores the adaptions of these satellites to their ever-evolving target phage.

show abstract

“…Pif1 family helicases are 5' to 3' superfamily 1 helicases that are highly conserved in most eukaryotes and some bacteria and are critical for DNA replication, recombination, and repair (BOCHMAN et al 2010;CHUNG 2014;BYRD AND RANEY 2017). Although Pif1 family helicases possess a conserved single-stranded (ss) DNA-dependent helicase domain, their N-and Cterminal domains differ significantly in size and sequence between organisms ( Figure S1) (LAHAYE et al 1991;BOULE AND ZAKIAN 2006).…”

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

View full text Add to dashboard Cite

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.

show abstract

Structure and function of Pif1 helicase

Cited by 56 publications

References 113 publications

The Pif1 signature motif of Pfh1 is necessary for both protein displacement and helicase unwinding activities, but is dispensable for strand-annealing activity

The Pif1 signature motif of Pfh1 is necessary for both protein displacement and helicase unwinding activities, but is dispensable for strand-annealing activity

Viral satellites exploit phage proteins to escape degradation of the bacterial host chromosome

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

Contact Info

Product

Resources

About