Mitochondrial transcription factor A promotes DNA strand cleavage at abasic sites.

Abstract:

:In higher eukaryotic cells, mitochondria are essential subcellular organelles for energy production, cell signaling, and the biosynthesis of biomolecules. The mitochondrial DNA (mtDNA) genome is indispensable for mitochondrial function because it encodes protein subunits of the electron transport chain and a full set of transfer and ribosomal RNAs. MtDNA degradation has emerged as an essential quality control measure to maintain mtDNA and to cope with mtDNA damage resulting from endogenous and environmental factors. Among all types of DNA damage known, abasic (AP) sites, sourced from base excision repair and spontaneous base loss, are the most abundant endogenous DNA lesions in cells. In mitochondria, AP sites trigger rapid DNA loss; however, the mechanism and molecular factors involved in the process remain elusive. Herein, we demonstrate that the stability of AP sites is reduced dramatically upon binding to a major mtDNA packaging protein, mitochondrial transcription factor A (TFAM). The half-life of AP lesions within TFAM-DNA complexes is 2 to 3 orders of magnitude shorter than that in free DNA, depending on their position. The TFAM-catalyzed AP-DNA destabilization occurs with nonspecific DNA or mitochondrial light-strand promoter sequence, yielding DNA single-strand breaks and DNA-TFAM cross-links. TFAM-DNA cross-link intermediates prior to the strand scission were also observed upon treating AP-DNA with mitochondrial extracts of human cells. In situ trapping of the reaction intermediates (DNA-TFAM cross-links) revealed that the reaction proceeds via Schiff base chemistry facilitated by lysine residues. Collectively, our data suggest a novel role of TFAM in facilitating the turnover of abasic DNA.

authors

Xu W,Boyd RM,Tree MO,Samkari F,Zhao L

doi

10.1073/pnas.1911252116

subject

Has Abstract

pub_date

2019-09-03 00:00:00

pages

17792-17799

issue

36

eissn

0027-8424

issn

1091-6490

pii

1911252116

journal_volume

116

pub_type

杂志文章
  • Nuclear uptake of 1,25-dihydroxy[3H]cholecalciferol in dispersed fibroblasts cultured from normal human skin.

    abstract::Because of the relative inaccessibility of known calciferol target tissues (i.e., intestine and bone), we examined fibroblasts derived from normal human skin and grown in tissue culture as a means of evaluating the interaction of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and its effector system. When dispersed, inta...

    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.78.4.2562

    authors: Eil C,Marx SJ

    更新日期:1981-04-01 00:00:00

  • Host-parasite relatedness shown by protein fingerprinting in a brood parasitic bird.

    abstract::Brood parasitism as an alternative female breeding tactic is particularly common in ducks, where hosts often receive eggs laid by parasitic females of the same species and raise their offspring. Herein, we test several aspects of a kin selection explanation for this phenomenon in goldeneye ducks (Bucephala clangula) b...

    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.220137897

    authors: Andersson M,Ahlund M

    更新日期:2000-11-21 00:00:00

  • Lazaroids improve the survival of grafted rat embryonic dopamine neurons.

    abstract::In rodent models of Parkinson disease in which transplants of dissociated rodent and human embryonic mesencephalic tissue, rich in dopamine neurons, have been studied, only 5-20% of the dopamine neurons survive the implantation procedure. We have investigated the effects of inhibiting free radical generation with two ...

    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.91.26.12408

    authors: Nakao N,Frodl EM,Duan WM,Widner H,Brundin P

    更新日期:1994-12-20 00:00:00

  • MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells.

    abstract::Canonical Wnt signaling plays an important role in development and disease, regulating transcription of target genes and stabilizing many proteins phosphorylated by glycogen synthase kinase 3 (GSK3). We observed that the MiT family of transcription factors, which includes the melanoma oncogene MITF (micropthalmia-asso...

    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.1424576112

    authors: Ploper D,Taelman VF,Robert L,Perez BS,Titz B,Chen HW,Graeber TG,von Euw E,Ribas A,De Robertis EM

    更新日期:2015-02-03 00:00:00

  • Crystallographic structure of a photoreceptor protein at 2.4 A resolution.

    abstract::The first essential step in protein photoreception is the capture and storage of energy from a photon. We have recently identified and isolated, from the purple photoautotrophic bacterium, Ectothiorhodospira halophila, a 13,000-dalton photoactive yellow protein (PYP) that has a photocycle with kinetics similar to sens...

    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.86.17.6533

    authors: McRee DE,Tainer JA,Meyer TE,Van Beeumen J,Cusanovich MA,Getzoff ED

    更新日期:1989-09-01 00:00:00

  • Aging reduces neural specialization in ventral visual cortex.

    abstract::The present study investigated whether neural structures become less functionally differentiated and specialized with age. We studied ventral visual cortex, an area of the brain that responds selectively to visual categories (faces, places, and words) in young adults, and that shows little atrophy with age. Functional...

    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.0405148101

    authors: Park DC,Polk TA,Park R,Minear M,Savage A,Smith MR

    更新日期:2004-08-31 00:00:00

  • A natural classification of the basic helix-loop-helix class of transcription factors.

    abstract::A natural (evolutionary) classification is provided for 242 basic helix-loop-helix (bHLH) motif-containing proteins. Phylogenetic analyses of amino acid sequences describe the patterns of evolutionary change within the motif and delimit evolutionary lineages. These evolutionary lineages represent well known functional...

    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.94.10.5172

    authors: Atchley WR,Fitch WM

    更新日期:1997-05-13 00:00:00

  • Importance of newly generated neurons in the adult olfactory bulb for odor discrimination.

    abstract::In adult rodents, neurons are continually generated in the subventricular zone of the forebrain, from where they migrate tangentially toward the olfactory bulb, the only known target for these neuronal precursors. Within the main olfactory bulb, they ascend radially into the granule and periglomerular cell layers, whe...

    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.97.4.1823

    authors: Gheusi G,Cremer H,McLean H,Chazal G,Vincent JD,Lledo PM

    更新日期:2000-02-15 00:00:00

  • Differential expression of SNAP-25 protein isoforms during divergent vesicle fusion events of neural development.

    abstract::The presynaptic plasma membrane protein SNAP-25 (synaptosome-associated protein of 25 kDa) has been implicated as one of several neural-specific components that direct constitutive fusion mechanisms to the regulated vesicle trafficking and exocytosis of neurotransmitter release. There exist two alternatively spliced 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.92.5.1510

    authors: Bark IC,Hahn KM,Ryabinin AE,Wilson MC

    更新日期:1995-02-28 00:00:00

  • Supercooled spin liquid state in the frustrated pyrochlore Dy2Ti2O7.

    abstract::A "supercooled" liquid develops when a fluid does not crystallize upon cooling below its ordering temperature. Instead, the microscopic relaxation times diverge so rapidly that, upon further cooling, equilibration eventually becomes impossible and glass formation occurs. Classic supercooled liquids exhibit specific id...

    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.1511006112

    authors: Kassner ER,Eyvazov AB,Pichler B,Munsie TJ,Dabkowska HA,Luke GM,Davis JC

    更新日期:2015-07-14 00:00:00

  • A general quantitative theory of forest structure and dynamics.

    abstract::We present the first part of a quantitative theory for the structure and dynamics of forests at demographic and resource steady state. The theory uses allometric scaling relations, based on metabolism and biomechanics, to quantify how trees use resources, fill space, and grow. These individual-level traits and propert...

    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.0812294106

    authors: West GB,Enquist BJ,Brown JH

    更新日期:2009-04-28 00:00:00

  • Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts.

    abstract::Drosophila neuroblasts divide asymmetrically by aligning their mitotic spindle with cortical cell polarity to generate distinct sibling cell types. Neuroblasts asymmetrically localize Galphai, Pins, and Mud proteins; Pins/Galphai direct cortical polarity, whereas Mud is required for spindle orientation. It is currentl...

    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.0701812104

    authors: Nipper RW,Siller KH,Smith NR,Doe CQ,Prehoda KE

    更新日期:2007-09-04 00:00:00

  • Mathematical analysis of locomotor behavior by mice in a radial maze.

    abstract::We investigated the effects of beta-estradiol on the locomotor behavior of female mice in a radial maze. Data comprising the total distance traveled during each arm entry were obtained from video records of six consecutive daily recording sessions. Distributions of these data were bimodal for both ovariectomized contr...

    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.0607258103

    authors: Coop AD,Stavarache MA,Pfaff DW,Reeke GN

    更新日期:2006-10-17 00:00:00

  • Positionally cloned human disease genes: patterns of evolutionary conservation and functional motifs.

    abstract::Positional cloning has already produced the sequences of more than 70 human genes associated with specific diseases. In addition to their medical importance, these genes are of interest as a set of human genes isolated solely on the basis of the phenotypic effect of the respective mutations. We analyzed the protein se...

    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.94.11.5831

    authors: Mushegian AR,Bassett DE Jr,Boguski MS,Bork P,Koonin EV

    更新日期:1997-05-27 00:00:00

  • Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion.

    abstract::Alphavirus envelope proteins, organized as trimers of E2-E1 heterodimers on the surface of the pathogenic alphavirus, mediate the low pH-triggered fusion of viral and endosomal membranes in human cells. The lack of specific treatment for alphaviral infections motivates our exploration of potential antiviral approaches...

    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.1414190112

    authors: Zeng X,Mukhopadhyay S,Brooks CL 3rd

    更新日期:2015-02-17 00:00:00

  • Theory of homogeneous dynamos in a rotating liquid sphere.

    abstract::A spherical harmonic analysis is made of the hydrodynamic equation governing the flow of an incompressible liquid in a rotating sphere in the presence of the magnetic Lorentz force. Nonlinear partial differential equations are derived for the functions S(n)(r,t) and T(n)(r,t) entering the spherical harmonic representa...

    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.72.4.1496

    authors: Pekeris CL,Accad Y

    更新日期:1975-04-01 00:00:00

  • Structure of the human hexabrachion (tenascin) gene.

    abstract::The structure of the gene encoding human hexabrachion (tenascin) has been determined from overlapping clones isolated from a human genomic bacteriophage library. The genomic inserts were characterized by restriction mapping, Southern blot analysis, PCR, and DNA sequencing. The coding region of the hexabrachion gene sp...

    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.88.21.9438

    authors: Gulcher JR,Nies DE,Alexakos MJ,Ravikant NA,Sturgill ME,Marton LS,Stefansson K

    更新日期:1991-11-01 00:00:00

  • Sparse bursts optimize information transmission in a multiplexed neural code.

    abstract::Many cortical neurons combine the information ascending and descending the cortical hierarchy. In the classical view, this information is combined nonlinearly to give rise to a single firing-rate output, which collapses all input streams into one. We analyze the extent to which neurons can simultaneously represent mul...

    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.1720995115

    authors: Naud R,Sprekeler H

    更新日期:2018-07-03 00:00:00

  • Antibody recognition of a unique tumor-specific glycopeptide antigen.

    abstract::Aberrant glycosylation and the overexpression of certain carbohydrate moieties is a consistent feature of cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy. One of the most common aberrations in glycosylation patterns is the presentation of a single O-linked N-acetyl...

    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.0915176107

    authors: Brooks CL,Schietinger A,Borisova SN,Kufer P,Okon M,Hirama T,Mackenzie CR,Wang LX,Schreiber H,Evans SV

    更新日期:2010-06-01 00:00:00

  • Identification, purification, and characterization of a zyxin-related protein that binds the focal adhesion and microfilament protein VASP (vasodilator-stimulated phosphoprotein).

    abstract::VASP (vasodilator-stimulated phosphoprotein), an established substrate of cAMP- and cGMP-dependent protein kinases in vitro and in living cells, is associated with focal adhesions, microfilaments, and membrane regions of high dynamic activity. Here, the identification of an 83-kDa protein (p83) that specifically binds...

    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.92.17.7956

    authors: Reinhard M,Jouvenal K,Tripier D,Walter U

    更新日期:1995-08-15 00:00:00

  • Overexpression of the chromosomally encoded aminoglycoside acetyltransferase eis confers kanamycin resistance in Mycobacterium tuberculosis.

    abstract::The emergence of multidrug-resistant (MDR) tuberculosis (TB) highlights the urgent need to understand the mechanisms of resistance to the drugs used to treat this disease. The aminoglycosides kanamycin and amikacin are important bactericidal drugs used to treat MDR TB, and resistance to one or both of these drugs is 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.0907925106

    authors: Zaunbrecher MA,Sikes RD Jr,Metchock B,Shinnick TM,Posey JE

    更新日期:2009-11-24 00:00:00

  • Structured clustering of the glycosphingolipid GM1 is required for membrane curvature induced by cholera toxin.

    abstract::AB5 bacterial toxins and polyomaviruses induce membrane curvature as a mechanism to facilitate their entry into host cells. How membrane bending is accomplished is not yet fully understood but has been linked to the simultaneous binding of the pentameric B subunit to multiple copies of glycosphingolipid receptors. Her...

    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.2001119117

    authors: Kabbani AM,Raghunathan K,Lencer WI,Kenworthy AK,Kelly CV

    更新日期:2020-06-30 00:00:00

  • Integration of light and abscisic acid signaling during seed germination and early seedling development.

    abstract::Seed germination is regulated by endogenous hormonal cues and external environmental stimuli such as water, low temperature, and light. After germination, the young seedling must rapidly establish its root system and the photoautotrophic capability appropriate to its surrounding environment. Light and the phytohormone...

    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.0710778105

    authors: Chen H,Zhang J,Neff MM,Hong SW,Zhang H,Deng XW,Xiong L

    更新日期:2008-03-18 00:00:00

  • Nucleotide sequence at the binding site for coat protein on RNA of bacteriophage R17.

    abstract::The binding of a few molecules [1-6] of RNA bacteriophage coat protein to 1 molecule of RNA represses in vitro translation of the RNA synthetase cistron. Digestion of the complex, R17 coat protein-R17 RNA, by T1 RNase yields an RNA fragment bound to the coat protein. The nucleotide sequence of this fragment (59 residu...

    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.69.10.3033

    authors: Bernardi A,Spahr PF

    更新日期:1972-10-01 00:00:00

  • Evidence for a rapid release of carbon at the Paleocene-Eocene thermal maximum.

    abstract::The Paleocene/Eocene thermal maximum (PETM) and associated carbon isotope excursion (CIE) are often touted as the best geologic analog for the current anthropogenic rise in pCO2. However, a causal mechanism for the PETM CIE remains unidentified because of large uncertainties in the duration of the CIE's onset. Here, w...

    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.1309188110

    authors: Wright JD,Schaller MF

    更新日期:2013-10-01 00:00:00

  • Transport direction determines the kinetics of substrate transport by the glutamate transporter EAAC1.

    abstract::Glutamate transport by the excitatory amino acid carrier EAAC1 is known to be reversible. Thus, glutamate can either be taken up into cells, or it can be released from cells through reverse transport, depending on the electrochemical gradient of the co- and countertransported ions. However, it is unknown how fast 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.0704570104

    authors: Zhang Z,Tao Z,Gameiro A,Barcelona S,Braams S,Rauen T,Grewer C

    更新日期:2007-11-13 00:00:00

  • Single-molecule spectroscopy reveals polymer effects of disordered proteins in crowded environments.

    abstract::Intrinsically disordered proteins (IDPs) are involved in a wide range of regulatory processes in the cell. Owing to their flexibility, their conformations are expected to be particularly sensitive to the crowded cellular environment. Here we use single-molecule Förster resonance energy transfer to quantify the effect ...

    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.1322611111

    authors: Soranno A,Koenig I,Borgia MB,Hofmann H,Zosel F,Nettels D,Schuler B

    更新日期:2014-04-01 00:00:00

  • Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression.

    abstract::Glucose is a fundamental metabolite, yet how cells sense and respond to changes in extracellular glucose concentration is not completely understood. We recently reported that the MondoA:Mlx dimeric transcription factor directly regulates glycolysis. In this article, we consider whether MondoA:Mlx complexes have a broa...

    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.0712199105

    authors: Stoltzman CA,Peterson CW,Breen KT,Muoio DM,Billin AN,Ayer DE

    更新日期:2008-05-13 00:00:00

  • Prosody guides the rapid mapping of auditory word forms onto visual objects in 6-mo-old infants.

    abstract::Human infants are predisposed to rapidly acquire their native language. The nature of these predispositions is poorly understood, but is crucial to our understanding of how infants unpack their speech input to recover the fundamental word-like units, assign them referential roles, and acquire the rules that govern the...

    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.1017617108

    authors: Shukla M,White KS,Aslin RN

    更新日期:2011-04-12 00:00:00

  • The Opitz syndrome gene product, MID1, associates with microtubules.

    abstract::Opitz syndrome (OS) is a genetically heterogeneous disorder characterized by defects of the ventral midline, including hypertelorism, cleft lip and palate, heart defects, and mental retardation. We recently identified the gene responsible for X-linked OS. The ubiquitously expressed gene product, MID1, is a member of 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.96.6.2794

    authors: Schweiger S,Foerster J,Lehmann T,Suckow V,Muller YA,Walter G,Davies T,Porter H,van Bokhoven H,Lunt PW,Traub P,Ropers HH

    更新日期:1999-03-16 00:00:00