Determination of the biochemical properties of full-length human PIF1 ATPase

Gu, Yongqing; Wang, Jianxiao; Li, Shanshan; Kamiya, Kenji; Chen, Xiaohua; Zhou, Ping

doi:10.4161/pri.26022

Cited by 5 publications

(5 citation statements)

References 31 publications

(49 reference statements)

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“…This significant yet partial R-loop-suppressing effect of Mg 2+ supplementation relative to that of CR is consistent with the differential increases in intracellular Mg 2+ levels under these two environmental conditions (Figure 1A , D , G and J ). Consistent with the sensitivity of Pif1 and RNaseH enzymes to changes in Mg 2+ but not Ca 2+ levels, Ca 2+ supplementation failed to counter R-loop buildup (Figure 1K ) ( 30 , 31 ). Preferential dependence of the highly conserved RNaseH enzymes on Mg 2+ over Ca 2+ stems from the small atomic radius and strict octahedral geometry of Mg 2+ allowing this ion to support critical enzymatic reaction intermediates (Supplementary Figure S1D and E) ( 33 ).…”

Section: Resultssupporting

confidence: 54%

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA–DNA hybrids

et al. 2016

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Dietary calorie restriction is a broadly acting intervention that extends the lifespan of various organisms from yeast to mammals. On another front, magnesium (Mg2+) is an essential biological metal critical to fundamental cellular processes and is commonly used as both a dietary supplement and treatment for some clinical conditions. If connections exist between calorie restriction and Mg2+ is unknown. Here, we show that Mg2+, acting alone or in response to dietary calorie restriction, allows eukaryotic cells to combat genome-destabilizing and lifespan-shortening accumulations of RNA–DNA hybrids, or R-loops. In an R-loop accumulation model of Pbp1-deficient Saccharomyces cerevisiae, magnesium ions guided by cell membrane Mg2+ transporters Alr1/2 act via Mg2+-sensitive R-loop suppressors Rnh1/201 and Pif1 to restore R-loop suppression, ribosomal DNA stability and cellular lifespan. Similarly, human cells deficient in ATXN2, the human ortholog of Pbp1, exhibit nuclear R-loop accumulations repressible by Mg2+ in a process that is dependent on the TRPM7 Mg2+ transporter and the RNaseH1 R-loop suppressor. Thus, we identify Mg2+ as a biochemical signal of beneficial calorie restriction, reveal an R-loop suppressing function for human ATXN2 and propose that practical magnesium supplementation regimens can be used to combat R-loop accumulation linked to the dysfunction of disease-linked human genes.

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Section: Resultssupporting

confidence: 54%

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA–DNA hybrids

et al. 2016

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“…Cdc24 depletion is thought to inactivate Dna2 functions in lagging strand DNA replication and DSB repair. Based on these findings, it was proposed that during OF processing, Pif1 creates a sub-population of long DNA flaps that must be processed by Dna2 (see below) [ 53 ], although the 5’–3’ directed DNA helicase activity of Pif1 would peel off the 3’ end of the newly synthesized fragment instead of displacing the 5’ end of the last OF [ 103 , 104 ]. This apparent discrepancy between the 5’–3’ polarity of Pif1 helicase and the processing of the 5’ ends of OFs can be rationalized if Pif1 is considered part of a strand displacement “machine” composed by PCNA-Pol δ-Pif1 (see below).…”

Section: The Replication Fork and The Dna Synthesis Apparatusmentioning

confidence: 99%

DNA Replication Through Strand Displacement During Lagging Strand DNA Synthesis in Saccharomyces cerevisiae

Giannattasio

Branzei

2019

Genes

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This review discusses a set of experimental results that support the existence of extended strand displacement events during budding yeast lagging strand DNA synthesis. Starting from introducing the mechanisms and factors involved in leading and lagging strand DNA synthesis and some aspects of the architecture of the eukaryotic replisome, we discuss studies on bacterial, bacteriophage and viral DNA polymerases with potent strand displacement activities. We describe proposed pathways of Okazaki fragment processing via short and long flaps, with a focus on experimental results obtained in Saccharomyces cerevisiae that suggest the existence of frequent and extended strand displacement events during eukaryotic lagging strand DNA synthesis, and comment on their implications for genome integrity.

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“…In addition, FLAG-tagged hPIF1 has been coimmunoprecipitated with Myc-tagged human telomerase catalytic subunit (hTERT) suggesting a physical interaction between these two enzymes and a role for hPIF1 in telomere metabolism [114]. Recently, the full-length hPIF1 has been successfully purified and biochemically characterized [118][119][120]. Deletion analysis has shown that the PIF1 N-terminal (PINT) domain significantly enhances ssDNA binding and also promotes DNA strand annealing [118].…”

Section: Pif1mentioning

confidence: 99%

“…The ATPase activity of the full-length hPIF1, which provides the energy to translocate along DNA and unwind the duplex DNA, has also been characterized. Binding to ssDNA greatly stimulates hPIF1 ATPase activity and this stimulation increases with an increasing length of ssDNA, due to an increase in hPIF1-ssDNA binding [120].…”

Section: Pif1mentioning

confidence: 99%

Mitochondrial DNA maintenance: an appraisal

Akhmedov

Marı́n-Garcı́a

2015

Mol Cell Biochem

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Mitochondria play a crucial role in a variety of cellular processes ranging from energy metabolism, generation of reactive oxygen species (ROS), and Ca(2+) handling to stress responses, cell survival, and death. Malfunction of the organelle may contribute to the pathogenesis of neuromuscular disorders, cancer, premature aging, and cardiovascular diseases, including myocardial ischemia, cardiomyopathy, and heart failure. Mitochondria are unique as they contain their own genome organized into DNA-protein complexes, so-called mitochondrial nucleoids, along with multiprotein machineries, which promote mitochondrial DNA (mtDNA) replication, transcription, and repair. Although the organelle possesses almost all known nuclear DNA repair pathways, including base excision repair, mismatch repair, and recombinational repair, the proximity of mtDNA to the main sites of ROS production and the lack of protective histones may result in increased susceptibility to oxidative stress and other types of mtDNA damage. Defects in the components of these highly organized machineries, which mediate mtDNA maintenance (replication and repair), may result in accumulation of point mutations and/or deletions in mtDNA and decreased mtDNA copy number impairing mitochondrial function. This review will focus on the mechanisms of mtDNA maintenance with emphasis on the proteins implicated in these processes and their functional role in various disease conditions and aging.

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Determination of the biochemical properties of full-length human PIF1 ATPase

Cited by 5 publications

References 31 publications

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA–DNA hybrids

Intersection of calorie restriction and magnesium in the suppression of genome-destabilizing RNA–DNA hybrids

DNA Replication Through Strand Displacement During Lagging Strand DNA Synthesis in Saccharomyces cerevisiae

Mitochondrial DNA maintenance: an appraisal

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