Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer.

Abstract:

:This article extends our previous quantitative analysis of the relationship between the dynamics of the primary structure of DNA and mutagenesis associated with single-strand lesions to an analysis of the production and processing of endogenous double-strand breaks (EDSBs) and to their implications for oncogenesis. We estimate that in normal human cells approximately 1% of single-strand lesions are converted to approximately 50 EDSBs per cell per cell cycle. This number is similar to that for EDSBs produced by 1.5-2.0 Gy of sparsely ionizing radiation. Although EDSBs are usually repaired with high fidelity, errors in their repair contribute significantly to the rate of cancer in humans. The doubling dose for induced DSBs is similar to doubling doses for mutation and for the induction of carcinomas by ionizing radiation. We conclude that rates of production of EDSBs and of ensuing spontaneous mitotic recombination events can account for a substantial fraction of the earliest oncogenic events in human carcinomas.

authors

Vilenchik MM,Knudson AG

doi

10.1073/pnas.2135498100

keywords:

subject

Has Abstract

pub_date

2003-10-28 00:00:00

pages

12871-6

issue

22

eissn

0027-8424

issn

1091-6490

pii

2135498100

journal_volume

100

pub_type

杂志文章
  • Hypoxia induces a time- and tissue-specific response that elicits intertissue circadian clock misalignment.

    abstract::The occurrence and sequelae of disorders that lead to hypoxic spells such as asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea (OSA) exhibit daily variance. This prompted us to examine the interaction between the hypoxic response and the circadian clock in vivo. We found that the global transc...

    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.1914112117

    authors: Manella G,Aviram R,Bolshette N,Muvkadi S,Golik M,Smith DF,Asher G

    更新日期:2020-01-07 00:00:00

  • On the stereochemistry and biosynthesis of lipoxin B.

    abstract::Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icos...

    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.83.7.1983

    authors: Serhan CN,Hamberg M,Samuelsson B,Morris J,Wishka DG

    更新日期:1986-04-01 00:00:00

  • Alternatively spliced tissue factor promotes breast cancer growth in a β1 integrin-dependent manner.

    abstract::Full-length tissue factor (flTF), the coagulation initiator, is overexpressed in breast cancer (BrCa), but associations between flTF expression and clinical outcome remain controversial. It is currently not known whether the soluble alternatively spliced TF form (asTF) is expressed in BrCa or impacts BrCa progression....

    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.1307100110

    authors: Kocatürk B,Van den Berg YW,Tieken C,Mieog JS,de Kruijf EM,Engels CC,van der Ent MA,Kuppen PJ,Van de Velde CJ,Ruf W,Reitsma PH,Osanto S,Liefers GJ,Bogdanov VY,Versteeg HH

    更新日期:2013-07-09 00:00:00

  • The spectrum of seminormal operators.

    abstract::With every pair of bounded self-adjoint operators {U,V} on Hilbert space such that VU - UV = (1/pii)C, where C is trace class, there is associated a certain function of two complex variables called the determining function of the pair. It was previously shown how the determining function can be obtained as the solutio...

    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.68.8.1684

    authors: Pincus JD

    更新日期:1971-08-01 00:00:00

  • Genomic evidence that the intracellular proteins of archaeal microbes contain disulfide bonds.

    abstract::Disulfide bonds have only rarely been found in intracellular proteins. That pattern is consistent with the chemically reducing environment inside the cells of well-studied organisms. However, recent experiments and new calculations based on genomic data of archaea provide striking contradictions to this pattern. Our r...

    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.142310499

    authors: Mallick P,Boutz DR,Eisenberg D,Yeates TO

    更新日期:2002-07-23 00:00:00

  • Uncoupling reproduction from metabolism extends chronological lifespan in yeast.

    abstract::Studies of replicative and chronological lifespan in Saccharomyces cerevisiae have advanced understanding of longevity in all eukaryotes. Chronological lifespan in this species is defined as the age-dependent viability of nondividing cells. To date this parameter has only been estimated under calorie restriction, mimi...

    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.1323918111

    authors: Nagarajan S,Kruckeberg AL,Schmidt KH,Kroll E,Hamilton M,McInnerney K,Summers R,Taylor T,Rosenzweig F

    更新日期:2014-04-15 00:00:00

  • Leukotriene B5 is formed in human neutrophils after dietary supplementation with icosapentaenoic acid.

    abstract::Incorporation and conversion of icosapentaenoic acid (20:5, n - 3) by human polymorphonuclear leukocytes were studied in volunteers (n = 6) ingesting a normal Western diet supplemented with icosapentaenoic acid (approximately equal to 4 g daily). Ingestion of icosapentaenoic acid leads to formation of biologically les...

    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.82.5.1540

    authors: Strasser T,Fischer S,Weber PC

    更新日期:1985-03-01 00:00:00

  • LFG: an anti-apoptotic gene that provides protection from Fas-mediated cell death.

    abstract::Programmed cell death regulates a number of biological phenomena, and the apoptotic signal must itself be tightly controlled to avoid inappropriate cell death. We established a genetic screen to search for molecules that inhibit the apoptotic signal from the Fas receptor. Here we report the isolation of a gene, LFG, 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.96.22.12667

    authors: Somia NV,Schmitt MJ,Vetter DE,Van Antwerp D,Heinemann SF,Verma IM

    更新日期:1999-10-26 00:00:00

  • General methodology for inferring failure-spreading dynamics in networks.

    abstract::A generic modeling framework to infer the failure-spreading process based on failure times of individual nodes is proposed and tested in four simulation studies: one for cascading failures in interdependent power and transportation networks, one for influenza epidemics, one benchmark test case for congestion cascade 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.1722313115

    authors: Guan X,Chen C

    更新日期:2018-08-28 00:00:00

  • Quest for life-long protection by vaccination.

    abstract::Life-long protection from disease through immunization can be accomplished through individual or community protection. Individual protection is the goal for vaccination against diseases that have inanimate or animal reservoirs or that pose risks for certain populations. Community protection is the goal for vaccination...

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

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.91.7.2464

    authors: Dowdle WR,Orenstein WA

    更新日期:1994-03-29 00:00:00

  • Photoperiod and temperature separately regulate nymphal development through JH and insulin/TOR signaling pathways in an insect.

    abstract::Insects living in the temperate zone enter a physiological state of arrested or slowed development to overcome an adverse season, such as winter. Developmental arrest, called diapause, occurs at a species-specific developmental stage, and embryonic and pupal diapauses have been extensively studied in mostly holometabo...

    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.1922747117

    authors: Miki T,Shinohara T,Chafino S,Noji S,Tomioka K

    更新日期:2020-03-10 00:00:00

  • Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality.

    abstract::Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors, and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within RBCs, thereby hiding themselves from direct contact and recognition by host imm...

    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.1316467111

    authors: Wu J,Tian L,Yu X,Pattaradilokrat S,Li J,Wang M,Yu W,Qi Y,Zeituni AE,Nair SC,Crampton SP,Orandle MS,Bolland SM,Qi CF,Long CA,Myers TG,Coligan JE,Wang R,Su XZ

    更新日期:2014-01-28 00:00:00

  • A single-stranded DNA-binding protein from Crithidia fasciculata recognizes the nucleotide sequence at the origin of replication of kinetoplast DNA minicircles.

    abstract::A sequence-specific single-stranded DNA-binding protein from the trypanosomatid protozoan Crithidia fasciculata binds to a sequence of 12 nucleotides located at the origin of replication of kinetoplast DNA minicircles. This sequence, termed the universal minicircle sequence (UMS), is conserved in the kinetoplast DNA m...

    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.89.15.6891

    authors: Tzfati Y,Abeliovich H,Kapeller I,Shlomai J

    更新日期:1992-08-01 00:00:00

  • Limits of multifunctionality in tunable networks.

    abstract::Nature is rife with networks that are functionally optimized to propagate inputs to perform specific tasks. Whether via genetic evolution or dynamic adaptation, many networks create functionality by locally tuning interactions between nodes. Here we explore this behavior in two contexts: strain propagation in mechanic...

    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.1806790116

    authors: Rocks JW,Ronellenfitsch H,Liu AJ,Nagel SR,Katifori E

    更新日期:2019-02-12 00:00:00

  • Nucleic acid-binding polymers as anti-inflammatory agents.

    abstract::Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundan...

    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.1105777108

    authors: Lee J,Sohn JW,Zhang Y,Leong KW,Pisetsky D,Sullenger BA

    更新日期:2011-08-23 00:00:00

  • Chromophore organization in photosynthetic reaction centers: High-resolution magnetophotoselection.

    abstract::The electron spin resonance spectrum of the triplet excited state of Rhodopseudomonas spheroides R-26 reaction centers has been studied after excitation with the polarized narrow-bandwidth output of a tunable dye laser from 520 to 670 nm. A theory is developed relating experimental observables to the angles between th...

    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.76.11.5636

    authors: Boxer SG,Roelofs MG

    更新日期:1979-11-01 00:00:00

  • Valinomycin-induced uptake of potassium in membrane vesicles from Escherichia coli.

    abstract::Osmotically shocked Escherichia coli and membrane vesicle ghosts from E. coli cells have lost the ability to accumulate potassium by active transport. The addition of valinomycin to the membrane ghosts restores the capacity to accumulate radioactive (42)K and (86)Rb by a temperature- and energy-dependent process. Memb...

    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.68.7.1488

    authors: Bhattacharyya P,Epstein W,Silver S

    更新日期:1971-07-01 00:00:00

  • Specific inhibition of herpes simplex virus DNA polymerase by helical peptides corresponding to the subunit interface.

    abstract::The herpes simplex virus DNA polymerase consists of two subunits--a catalytic subunit and an accessory subunit, UL42, that increases processivity. Mutations affecting the extreme C terminus of the catalytic subunit specifically disrupt subunit interactions and ablate virus replication, suggesting that new antiviral dr...

    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.92.5.1456

    authors: Digard P,Williams KP,Hensley P,Brooks IS,Dahl CE,Coen DM

    更新日期:1995-02-28 00:00:00

  • Escherichia coli mutS-encoded protein binds to mismatched DNA base pairs.

    abstract::The Escherichia coli mutS gene product is involved in mismatch correction in this organism. We have purified a biologically active form of the 97,000 Mr protein to near homogeneity from an overproducing strain. Enzymatic and chemical protection ("footprinting") experiments have demonstrated that mutS-encoded protein 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.83.14.5057

    authors: Su SS,Modrich P

    更新日期:1986-07-01 00:00:00

  • Antibodies in human serum that precipitate ribonuclease P.

    abstract::Sera from certain patients with systemic lupus erythematosus (SLE) and related rheumatic diseases contain antibodies that selectively deplete extracts of HeLa cells of RNase P activity. Most of the sera that recognize RNase P, an endoribonuclease with an essential RNA subunit, also contain antibodies against another 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.85.15.5483

    authors: Gold HA,Craft J,Hardin JA,Bartkiewicz M,Altman S

    更新日期:1988-08-01 00:00:00

  • Transit-time and age distributions for nonlinear time-dependent compartmental systems.

    abstract::Many processes in nature are modeled using compartmental systems (reservoir/pool/box systems). Usually, they are expressed as a set of first-order differential equations describing the transfer of matter across a network of compartments. The concepts of age of matter in compartments and the time required for particles...

    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.1705296115

    authors: Metzler H,Müller M,Sierra CA

    更新日期:2018-02-06 00:00:00

  • DNA typing in thirty seconds with a microfabricated device.

    abstract::We report the development of a practical ultrafast allelic profiling assay for the analysis of short tandem repeats (STRs) by using a highly optimized microfluidic electrophoresis device. We have achieved baseline-resolved electrophoretic separations of single-locus STR samples in 30 sec. Analyses of PCR samples conta...

    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.94.19.10273

    authors: Schmalzing D,Koutny L,Adourian A,Belgrader P,Matsudaira P,Ehrlich D

    更新日期:1997-09-16 00:00:00

  • Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer.

    abstract::Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves 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.1802354115

    authors: Lee JK,Bangayan NJ,Chai T,Smith BA,Pariva TE,Yun S,Vashisht A,Zhang Q,Park JW,Corey E,Huang J,Graeber TG,Wohlschlegel J,Witte ON

    更新日期:2018-05-08 00:00:00

  • Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells.

    abstract::Capsaicin (CP), the pungent component of chili pepper, acts on sensory neurons to convey the sensation of pain. The CP receptor, vanilloid receptor 1 (VR1), has been shown to be highly expressed by nociceptive neurons in dorsal root and trigeminal ganglia. We demonstrate here that the dendritic cell (DC), a key cell 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.0407780102

    authors: Basu S,Srivastava P

    更新日期:2005-04-05 00:00:00

  • Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas.

    abstract::CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different...

    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.96.5.1977

    authors: Buters JT,Sakai S,Richter T,Pineau T,Alexander DL,Savas U,Doehmer J,Ward JM,Jefcoate CR,Gonzalez FJ

    更新日期:1999-03-02 00:00:00

  • Fusigenic viral liposome for gene therapy in cardiovascular diseases.

    abstract::To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) are complexed with liposomes that encapsulate oligodeoxynucleot...

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

    pub_type: 评论,杂志文章,评审

    doi:10.1073/pnas.93.21.11421

    authors: Dzau VJ,Mann MJ,Morishita R,Kaneda Y

    更新日期:1996-10-15 00:00:00

  • A murine fibroblast growth factor (FGF) receptor expressed in CHO cells is activated by basic FGF and Kaposi FGF.

    abstract::We have cloned a murine cDNA encoding a tyrosine kinase receptor with about 90% similarity to the chicken fibroblast growth factor (FGF) receptor and the human fms-like gene (FLG) tyrosine kinase. This mouse receptor lacks 88 amino acids in the extracellular portion, leaving only two immunoglobulin-like domains compar...

    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.87.11.4378

    authors: Mansukhani A,Moscatelli D,Talarico D,Levytska V,Basilico C

    更新日期:1990-06-01 00:00:00

  • Detection and isolation of a new DNA polymerase from human breast tumor cell line HBT-3 by (dT)12-18-cellulose chromatography.

    abstract::Column chromatography on (dT)(12-18)-cellulose was used to detect and isolate a novel DNA polymerase activity from human breast tumor cell line HBT-3. The new enzyme is similar to those of mammalian RNA tumor viruses in its molecular size, preference for poly(A).(dT)(12-18) as compared to either poly(dA).(dT)(12-18) 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.70.8.2453

    authors: Gerwin BI,Bassin RH

    更新日期:1973-08-01 00:00:00

  • Reversal of DNA alkylation damage by two human dioxygenases.

    abstract::The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA. AlkB is an alpha-ketoglutarate- and Fe(II)-dependent dioxygenase that oxidizes the relevant methyl groups...

    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.262589799

    authors: Duncan T,Trewick SC,Koivisto P,Bates PA,Lindahl T,Sedgwick B

    更新日期:2002-12-24 00:00:00

  • Physical map of human Xq27-qter: localizing the region of the fragile X mutation.

    abstract::We describe a physical map of the end of the long arm of the human X chromosome encompassing the region from Xq27.2 to the q telomere, inclusive of the chromosomal band Xq28. This region is of particular interest, since it contains the highest density of genes associated with genetic diseases. The map covers a total 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.88.19.8302

    authors: Poustka A,Dietrich A,Langenstein G,Toniolo D,Warren ST,Lehrach H

    更新日期:1991-10-01 00:00:00