Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.

Abstract:

:Encoding ribonuclease H1 (RNase H1) degrades RNA hybridized to DNA, and its function is essential for mitochondrial DNA maintenance in the developing mouse. Here we define the role of RNase H1 in mitochondrial DNA replication. Analysis of replicating mitochondrial DNA in embryonic fibroblasts lacking RNase H1 reveals retention of three primers in the major noncoding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L. Primer retention does not lead immediately to depletion, as the persistent RNA is fully incorporated in mitochondrial DNA. However, the retained primers present an obstacle to the mitochondrial DNA polymerase γ in subsequent rounds of replication and lead to the catastrophic generation of a double-strand break at the origin when the resulting gapped molecules are copied. Hence, the essential role of RNase H1 in mitochondrial DNA replication is the removal of primers at the origin of replication.

authors

Holmes JB,Akman G,Wood SR,Sakhuja K,Cerritelli SM,Moss C,Bowmaker MR,Jacobs HT,Crouch RJ,Holt IJ

doi

10.1073/pnas.1503653112

subject

Has Abstract

pub_date

2015-07-28 00:00:00

pages

9334-9

issue

30

eissn

0027-8424

issn

1091-6490

pii

1503653112

journal_volume

112

pub_type

杂志文章
  • Rate enhancement of reconstitution of glyceraldehyde-3-phosphate dehydrogenase by a covalently bound coenzyme analog.

    abstract::Kinetic analysis of the in vitro reconstitution of glyceraldehyde-3-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12] from yeast showed that both oxidized and reduced coenzyme enhance the transconformation reaction, which is rate limiting in the sequential foldin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.77.4.1966

    authors: Jaenicke R,Krebs H,Rudolph R,Woenckhaus C

    更新日期:1980-04-01 00:00:00

  • A genome-scale CRISPR screen reveals factors regulating Wnt-dependent renewal of mouse gastric epithelial cells.

    abstract::An ability to safely harness the powerful regenerative potential of adult stem cells for clinical applications is critically dependent on a comprehensive understanding of the underlying mechanisms regulating their activity. Epithelial organoid cultures accurately recapitulate many features of in vivo stem cell-driven ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2016806118

    authors: Murakami K,Terakado Y,Saito K,Jomen Y,Takeda H,Oshima M,Barker N

    更新日期:2021-01-26 00:00:00

  • Evolution of a mass spectrometry-grade protease with PTM-directed specificity.

    abstract::Mapping posttranslational modifications (PTMs), which diversely modulate biological functions, represents a significant analytical challenge. The centerpiece technology for PTM site identification, mass spectrometry (MS), requires proteolytic cleavage in the vicinity of a PTM to yield peptides for sequencing. This req...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1609925113

    authors: Tran DT,Cavett VJ,Dang VQ,Torres HL,Paegel BM

    更新日期:2016-12-20 00:00:00

  • TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation.

    abstract::Down-regulation of mitogenic signaling in mammalian cells relies in part on endosomal trafficking of activated receptors into lysosomes, where the receptors are degraded. These events are mediated by ubiquitination of the endosomal cargo and its consequent sorting into multivesicular bodies that form at the surfaces o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0932599100

    authors: Lu Q,Hope LW,Brasch M,Reinhard C,Cohen SN

    更新日期:2003-06-24 00:00:00

  • The Na+/I symporter (NIS) mediates electroneutral active transport of the environmental pollutant perchlorate.

    abstract::The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that mediates active I(-) uptake in the thyroid, lactating breast, and other tissues with an electrogenic stoichiometry of 2 Na(+) per I(-). In the thyroid, NIS-mediated I(-) uptake is the first step in the biosynthesis of the iodine-containing thyroid ho...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0707207104

    authors: Dohán O,Portulano C,Basquin C,Reyna-Neyra A,Amzel LM,Carrasco N

    更新日期:2007-12-18 00:00:00

  • Structure of the trypanosome haptoglobin-hemoglobin receptor and implications for nutrient uptake and innate immunity.

    abstract::African trypanosomes are protected by a densely packed surface monolayer of variant surface glycoprotein (VSG). A haptoglobin-hemoglobin receptor (HpHbR) within this VSG coat mediates heme acquisition. HpHbR is also exploited by the human host to mediate endocytosis of trypanolytic factor (TLF)1 from serum, contributi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1214943110

    authors: Higgins MK,Tkachenko O,Brown A,Reed J,Raper J,Carrington M

    更新日期:2013-01-29 00:00:00

  • ACHT4-driven oxidation of APS1 attenuates starch synthesis under low light intensity in Arabidopsis plants.

    abstract::The regulatory mechanisms that use signals of low levels of reactive oxygen species (ROS) could be obscured by ROS produced under stress and thus are better investigated under homeostatic conditions. Previous studies showed that the chloroplastic atypical thioredoxin ACHT1 is oxidized by 2-Cys peroxiredoxin (2-Cys Prx...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1515513112

    authors: Eliyahu E,Rog I,Inbal D,Danon A

    更新日期:2015-10-13 00:00:00

  • Rosiglitazone increases dendritic spine density and rescues spine loss caused by apolipoprotein E4 in primary cortical neurons.

    abstract::Convergent evidence has revealed an association between insulin resistance and Alzheimer's disease (AD), and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, rosiglitazone, an insulin sensitizer and mitochondrial activator, improves cognition in patients with early or mild-to-moderate AD. Apo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0709906104

    authors: Brodbeck J,Balestra ME,Saunders AM,Roses AD,Mahley RW,Huang Y

    更新日期:2008-01-29 00:00:00

  • The compression hypothesis and temporal resource partitioning.

    abstract::Contingency models of feeding compare the energy per unit time gained from utilizing a resource unit of a particular kind (food types, habitat patches, time periods) against that energy/time expected if the unit is skipped. Optimally, an animal should reject the particular unit if and only if the former energy/time is...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.10.4169

    authors: Schoener TW

    更新日期:1974-10-01 00:00:00

  • Bacterial growth and motility in sub-micron constrictions.

    abstract::In many naturally occurring habitats, bacteria live in micrometer-size confined spaces. Although bacterial growth and motility in such constrictions is of great interest to fields as varied as soil microbiology, water purification, and biomedical research, quantitative studies of the effects of confinement on bacteria...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907542106

    authors: Männik J,Driessen R,Galajda P,Keymer JE,Dekker C

    更新日期:2009-09-01 00:00:00

  • Noninvasive molecular imaging of c-Myc activation in living mice.

    abstract::The cytoplasmic Myc protein (c-Myc) regulates various human genes and is dysregulated in many human cancers. Phosphorylation mediates the protein activation of c-Myc and is essential for the function of this transcription factor in normal cell behavior and tumor growth. To date, however, the targeting of Myc as a ther...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1007443107

    authors: Fan-Minogue H,Cao Z,Paulmurugan R,Chan CT,Massoud TF,Felsher DW,Gambhir SS

    更新日期:2010-09-07 00:00:00

  • Translocation of protein kinase C in human leukemia cells susceptible or resistant to differentiation induced by phorbol 12-myristate 13-acetate.

    abstract::We investigated the possible relationship between the susceptibility of cells to differentiation induced by phorbol 12-myristate 13-acetate (PMA) and the subcellular translocation of calcium- and phospholipid-dependent protein kinase (protein kinase C) activity from the cytosol to the membrane. These two events were a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.19.7316

    authors: Homma Y,Henning-Chubb CB,Huberman E

    更新日期:1986-10-01 00:00:00

  • Phosphate metabolism in intact human erythrocytes: determination by phosphorus-31 nuclear magnetic resonance spectroscopy.

    abstract::Whole human blood was examined by (31)P nuclear magnetic resonance spectroscopy. Individual phosphates (alpha,beta,gamma) of ATP were identifiable, and two microenvironments appeared to be present for this molecule. When sequential recordings of freshly collected blood were made, 2,3-diphosphoglycerate was observed to...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.6.2487

    authors: Henderson TO,Costello AJ,Omachi A

    更新日期:1974-06-01 00:00:00

  • The replication initiation protein of the broad-host-range plasmid RK2 is activated by the ClpX chaperone.

    abstract::Initiation and control of replication of the broad-host-range plasmid RK2 requires two plasmid-encoded elements, the replication origin (oriV) and the initiation protein TrfA. Purified TrfA is largely in the form of a dimer; however, only the monomeric form of the protein can bind specifically to the direct repeats (i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.26.14378

    authors: Konieczny I,Helinski DR

    更新日期:1997-12-23 00:00:00

  • Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine.

    abstract::An isoform of the mammalian renal type II Na/Pi-cotransporter is described. Homology of this isoform to described mammalian and nonmammalian type II cotransporters is between 57 and 75%. Based on major diversities at the C terminus, the new isoform is designed as type IIb Na/Pi-cotransporter. Na/Pi-cotransport mediate...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.24.14564

    authors: Hilfiker H,Hattenhauer O,Traebert M,Forster I,Murer H,Biber J

    更新日期:1998-11-24 00:00:00

  • Schwann cell proliferation and localized proteolysis: expression of plasminogen-activator activity predominates in the proliferating cell populations.

    abstract::The role of the serum proteolytic system plasminogen/plasminogen activator as a biochemical tool used by the glia or neurons, or both, for maintaining their temporary and flexible cellular interactions during histogenesis of the nervous system is under study. The present report identifies a glia cell type, the Schwann...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.22.7216

    authors: Kalderon N

    更新日期:1984-11-01 00:00:00

  • The protracted Holocene extinction of California's flightless sea duck (Chendytes lawi) and its implications for the Pleistocene overkill hypothesis.

    abstract::Bones of the flightless sea duck (Chendytes lawi) from 14 archaeological sites along the California coast indicate that humans hunted the species for at least 8,000 years before it was driven to extinction. Direct (14)C dates on Chendytes bones show that the duck was exploited on the southern California islands as ear...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.0711140105

    authors: Jones TL,Porcasi JF,Erlandson JM,Dallas H Jr,Wake TA,Schwaderer R

    更新日期:2008-03-18 00:00:00

  • Substrate-induced conformational change in a trimeric ornithine transcarbamoylase.

    abstract::The crystal structure of Escherichia coli ornithine transcarbamoylase (OTCase, EC 2.1.3.3) complexed with the bisubstrate analog N-(phosphonacetyl)-L-ornithine (PALO) has been determined at 2.8-A resolution. This research on the structure of a transcarbamoylase catalytic trimer with a substrate analog bound provides n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.18.9550

    authors: Ha Y,McCann MT,Tuchman M,Allewell NM

    更新日期:1997-09-02 00:00:00

  • Intracellular injection of protein kinase inhibitor blocks the serotonin-induced increase in K+ conductance in Aplysia neuron R15.

    abstract::Previous work has shown that serotonin induces an increase in membrane K+ conductance in Aplysia neuron R15 and that this response is mediated by cAMP. The present study examines the role of protein phosphorylation in the response to serotonin. A specific inhibitor of cAMP-dependent protein kinase was injected intrace...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.12.3877

    authors: Adams WB,Levitan IB

    更新日期:1982-06-01 00:00:00

  • A TNFSF15 disease-risk polymorphism increases pattern-recognition receptor-induced signaling through caspase-8-induced IL-1.

    abstract::Inflammatory diseases are characterized by dysregulated cytokine production. Altered functions for most risk loci, including the inflammatory bowel disease and leprosy-associated tumor necrosis factor ligand superfamily member 15 (TNFSF15) region, are unclear. Regulation of pattern-recognition-receptor (PRR)-induced s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1404178111

    authors: Hedl M,Abraham C

    更新日期:2014-09-16 00:00:00

  • Direct photoaffinity labeling of tubulin with colchicine.

    abstract::Ultraviolet irradiation of the [3H]colchicine-tubulin complex leads to direct photolabeling of tubulin with low but practicable efficiency. The bulk (70% to greater than 90%) of the labeling occurs on beta-tubulin and appears early after irradiation, whereas alpha-tubulin is labeled later. The labeling ratio of beta-t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.7.2820

    authors: Wolff J,Knipling L,Cahnmann HJ,Palumbo G

    更新日期:1991-04-01 00:00:00

  • Surveying the sequence diversity of model prebiotic peptides by mass spectrometry.

    abstract::The rise of peptides with secondary structures and functions would have been a key step in the chemical evolution which led to life. As with modern biology, amino acid sequence would have been a primary determinant of peptide structure and activity in an origins-of-life scenario. It is a commonly held hypothesis that ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1711631114

    authors: Forsythe JG,Petrov AS,Millar WC,Yu SS,Krishnamurthy R,Grover MA,Hud NV,Fernández FM

    更新日期:2017-09-12 00:00:00

  • Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases.

    abstract::The ras oncogene products require membrane localization for their function, and this is thought to be accomplished by the addition of a palmitoyl group to a cysteine residue near the carboxyl terminus of the nascent chain. A lipidated carboxyl-terminal cysteine residue is also found in sequence-related yeast sex facto...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.13.4643

    authors: Clarke S,Vogel JP,Deschenes RJ,Stock J

    更新日期:1988-07-01 00:00:00

  • A putative ATP-dependent RNA helicase involved in Saccharomyces cerevisiae ribosome assembly.

    abstract::We have isolated a cold-sensitive mutant of Saccharomyces cerevisiae in which there is a deficit of 60S ribosomal subunits. Cold sensitivity and the assembly defect are recessive and cosegregate, defining a single essential gene that we designated DRS1 (deficiency of ribosomal subunits). The wild-type DRS1 gene was cl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.23.11131

    authors: Ripmaster TL,Vaughn GP,Woolford JL Jr

    更新日期:1992-12-01 00:00:00

  • Circular dichroism and magnetic circular dichroism of nitrogenase proteins.

    abstract::Circular dichroism (CD) and magnetic circular dichroism (MCD) spectra of nitrogenase components (MoFe protein and Fe protein) from Azotobacter vinelandii (Av) and Klebsiella pneumoniae (Kp) have been obtained in the near infrared-visible-near ultraviolet spectral region. Previously, visible CD was reported to be absen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.6.2585

    authors: Stephens PJ,McKenna CE,Smith BE,Nguyen HT,McKenna MC,Thomson AJ,Devlin F,Jones JB

    更新日期:1979-06-01 00:00:00

  • Random phase detection in multidimensional NMR.

    abstract::Despite advances in resolution accompanying the development of high-field superconducting magnets, biomolecular applications of NMR require multiple dimensions in order to resolve individual resonances, and the achievable resolution is typically limited by practical constraints on measuring time. In addition to the ne...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1103723108

    authors: Maciejewski MW,Fenwick M,Schuyler AD,Stern AS,Gorbatyuk V,Hoch JC

    更新日期:2011-10-04 00:00:00

  • A soluble domain of the membrane-anchoring chain of influenza virus hemagglutinin (HA2) folds in Escherichia coli into the low-pH-induced conformation.

    abstract::The extensive refolding of the membrane-anchoring chain of hemagglutinin (HA) of influenza virus (termed HA2) in cellular endosomes, which initiates viral entry by membrane fusion, suggests that viral HA is meta-stable. HA2 polypeptide residues 38-175 expressed in Escherichia coli are reported here to fold in vivo int...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.26.12205

    authors: Chen J,Wharton SA,Weissenhorn W,Calder LJ,Hughson FM,Skehel JJ,Wiley DC

    更新日期:1995-12-19 00:00:00

  • Quantifying the driving factors for language shift in a bilingual region.

    abstract::Many of the world's around 6,000 languages are in danger of disappearing as people give up use of a minority language in favor of the majority language in a process called language shift. Language shift can be monitored on a large scale through the use of mathematical models by way of differential equations, for examp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1617252114

    authors: Prochazka K,Vogl G

    更新日期:2017-04-25 00:00:00

  • Opposing effects of estradiol and progesterone on oxytocin receptors in rabbit uterus.

    abstract::Estradiol-17beta administration to young (10- to 12-week-old) rabbits to produce the "estrogen-dominated" uterus increased the uterine contractile response to both oxytocin and methacholine in vitro. In "progesterone-dominated" uteri, obtained from rabbits that received progesterone for 4 days after estrogen pretreatm...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.4.2044

    authors: Nissenson R,Fluoret G,Hechter O

    更新日期:1978-04-01 00:00:00

  • Structures of complexes comprised of Fischerella transcription factor HetR with Anabaena DNA targets.

    abstract::HetR is an essential regulator of heterocyst development in cyanobacteria. Many mutations in HetR render Anabaena incapable of nitrogen fixation. The protein binds to a DNA palindrome upstream of hetP and other genes. We have determined the crystal structures of HetR complexed with palindromic DNA targets, 21, 23, and...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1305971110

    authors: Kim Y,Ye Z,Joachimiak G,Videau P,Young J,Hurd K,Callahan SM,Gornicki P,Zhao J,Haselkorn R,Joachimiak A

    更新日期:2013-05-07 00:00:00