当前位置： SCI文献检索 > NATURE GENETICS期刊下所有文献 > Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations.

Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations.

Abstract：

:Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity and DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutation remain unknown. Here, we show that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Transcription-coupled DNA repair removes lesions on the transcribed strand; lesions on the non-transcribed strand are preferentially converted into mutations. In human polymorphism we detect a striking similarity between mutation types predominant on the non-transcribed strand and on the strand lagging during replication. Moreover, damage-induced mutations in cancers accumulate asymmetrically with respect to the direction of replication, suggesting that DNA lesions are resolved asymmetrically. We experimentally demonstrate that replication delay greatly attenuates the mutagenic effect of ultraviolet irradiation, confirming that replication converts DNA damage into mutations. We estimate that at least 10% of human mutations arise due to DNA damage.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Seplyarskiy VB,Akkuratov EE,Akkuratova N,Andrianova MA,Nikolaev SI,Bazykin GA,Adameyko I,Sunyaev SR

doi

10.1038/s41588-018-0285-7

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

36-41

issue

1

eissn

1061-4036

issn

1546-1718

pii

10.1038/s41588-018-0285-7

journal_volume

51

pub_type

杂志文章

相关文献

NATURE GENETICS文献大全
  • LD Score regression distinguishes confounding from polygenicity in genome-wide association studies.

    abstract：:Both polygenicity (many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from a true polygenic signal a...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3211

    authors： Bulik-Sullivan BK,Loh PR,Finucane HK,Ripke S,Yang J,Schizophrenia Working Group of the Psychiatric Genomics Consortium.,Patterson N,Daly MJ,Price AL,Neale BM

    更新日期：2015-03-01 00:00:00

  • Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome.

    abstract：:Joubert syndrome-related disorders (JSRD) are a group of syndromes sharing the neuroradiological features of cerebellar vermis hypoplasia and a peculiar brainstem malformation known as the 'molar tooth sign'. We identified mutations in the CEP290 gene in five families with variable neurological, retinal and renal mani...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1805

    authors： Valente EM,Silhavy JL,Brancati F,Barrano G,Krishnaswami SR,Castori M,Lancaster MA,Boltshauser E,Boccone L,Al-Gazali L,Fazzi E,Signorini S,Louie CM,Bellacchio E,International Joubert Syndrome Related Disorders Study Group.,B

    更新日期：2006-06-01 00:00:00

  • Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas.

    abstract：:Many individuals with multiple or large colorectal adenomas or early-onset colorectal cancer (CRC) have no detectable germline mutations in the known cancer predisposition genes. Using whole-genome sequencing, supplemented by linkage and association analysis, we identified specific heterozygous POLE or POLD1 germline ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2503

    authors： Palles C,Cazier JB,Howarth KM,Domingo E,Jones AM,Broderick P,Kemp Z,Spain SL,Guarino E,Salguero I,Sherborne A,Chubb D,Carvajal-Carmona LG,Ma Y,Kaur K,Dobbins S,Barclay E,Gorman M,Martin L,Kovac MB,Humphray S,COR

    更新日期：2013-02-01 00:00:00

  • Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly.

    abstract：:May-Hegglin anomaly (MHA) is an autosomal dominant macrothrombocytopenia of unclear pathogenesis characterized by thrombocytopenia, giant platelets and leukocyte inclusions. Studies have indicated that platelet structure and function are normal, suggesting a defect in megakaryocyte fragmentation. The disorder has been...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/79069

    authors： Kelley MJ,Jawien W,Ortel TL,Korczak JF

    更新日期：2000-09-01 00:00:00

  • Physical mapping of the holoprosencephaly critical region on chromosome 7q36.

    abstract：:Holoprosencephaly (HPE) is a developmental field defect involving the brain and face. Cytogenetic deletions in patients with HPE have localized one of the HPE genes to chromosomal region 7q36. We have characterized the 7q deletions in thirteen HPE patients. The result is the construction of a high resolution physical ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0393-247

    authors： Gurrieri F,Trask BJ,van den Engh G,Krauss CM,Schinzel A,Pettenati MJ,Schindler D,Dietz-Band J,Vergnaud G,Scherer SW

    更新日期：1993-03-01 00:00:00

  • Transcription imparts architecture, function and logic to enhancer units.

    abstract：:Distal enhancers play pivotal roles in development and disease yet remain one of the least understood regulatory elements. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites are robust predictors of active enha...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-020-0686-2

    authors： Tippens ND,Liang J,Leung AK,Wierbowski SD,Ozer A,Booth JG,Lis JT,Yu H

    更新日期：2020-10-01 00:00:00

  • Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin.

    abstract：:Friedreich's ataxia is due to loss of function mutations in the gene encoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected f...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0897-345

    authors： Koutnikova H,Campuzano V,Foury F,Dollé P,Cazzalini O,Koenig M

    更新日期：1997-08-01 00:00:00

  • Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia.

    abstract：:To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the abse...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/8751

    authors： Rane SG,Dubus P,Mettus RV,Galbreath EJ,Boden G,Reddy EP,Barbacid M

    更新日期：1999-05-01 00:00:00

  • DNA methylation loss in late-replicating domains is linked to mitotic cell division.

    abstract：:DNA methylation loss occurs frequently in cancer genomes, primarily within lamina-associated, late-replicating regions termed partially methylated domains (PMDs). We profiled 39 diverse primary tumors and 8 matched adjacent tissues using whole-genome bisulfite sequencing (WGBS) and analyzed them alongside 343 addition...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0073-4

    authors： Zhou W,Dinh HQ,Ramjan Z,Weisenberger DJ,Nicolet CM,Shen H,Laird PW,Berman BP

    更新日期：2018-04-01 00:00:00

  • Contribution of the FMR1 gene mutation to human intellectual dysfunction.

    abstract：:The degree to which genetic factors influence human intelligence remains a matter of some controversy. However, there is little doubt that single gene mutations can significantly alter brain development and function. For example, mutations affecting the FMR1 gene cause the fragile X syndrome, the most prevalent known ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1195-331

    authors： Reiss AL,Freund LS,Baumgardner TL,Abrams MT,Denckla MB

    更新日期：1995-11-01 00:00:00

  • Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa.

    abstract：:A highly invasive form of non-typhoidal Salmonella (iNTS) disease has recently been documented in many countries in sub-Saharan Africa. The most common Salmonella enterica serovar causing this disease is Typhimurium (Salmonella Typhimurium). We applied whole-genome sequence-based phylogenetic methods to define the pop...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2423

    authors： Okoro CK,Kingsley RA,Connor TR,Harris SR,Parry CM,Al-Mashhadani MN,Kariuki S,Msefula CL,Gordon MA,de Pinna E,Wain J,Heyderman RS,Obaro S,Alonso PL,Mandomando I,MacLennan CA,Tapia MD,Levine MM,Tennant SM,Parkhill J,

    更新日期：2012-11-01 00:00:00

  • Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis.

    abstract：:Animal models indicate that the antimicrobial peptide hepcidin (HAMP; OMIM 606464) is probably a key regulator of iron absorption in mammals. Here we report the identification of two mutations (93delG and 166C-->T) in HAMP on 19q13 in two families with a new type of juvenile hemochromatosis. ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1053

    authors： Roetto A,Papanikolaou G,Politou M,Alberti F,Girelli D,Christakis J,Loukopoulos D,Camaschella C

    更新日期：2003-01-01 00:00:00

  • Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1.

    abstract：:The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Han...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0398-266

    authors： Firulli AB,McFadden DG,Lin Q,Srivastava D,Olson EN

    更新日期：1998-03-01 00:00:00

  • A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis.

    abstract：:The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) a...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/3034

    authors： Strautnieks SS,Bull LN,Knisely AS,Kocoshis SA,Dahl N,Arnell H,Sokal E,Dahan K,Childs S,Ling V,Tanner MS,Kagalwalla AF,Németh A,Pawlowska J,Baker A,Mieli-Vergani G,Freimer NB,Gardiner RM,Thompson RJ

    更新日期：1998-11-01 00:00:00

  • Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis.

    abstract：:The GM2 gangliosidoses, Tay-Sachs and Sandhoff diseases, are caused by mutations in the HEXA (alpha-subunit) and HEXB (beta-subunit) genes, respectively. Each gene encodes a subunit for the heterodimeric lysosomal enzyme, beta-hexosaminidase A (alpha beta), as well as for the homodimers beta-hexosaminidase B (beta bet...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1196-348

    authors： Sango K,McDonald MP,Crawley JN,Mack ML,Tifft CJ,Skop E,Starr CM,Hoffmann A,Sandhoff K,Suzuki K,Proia RL

    更新日期：1996-11-01 00:00:00

  • A genetic link between cold responses and flowering time through FVE in Arabidopsis thaliana.

    abstract：:Cold induces expression of a number of genes that encode proteins that enhance tolerance to freezing temperatures in plants. A cis-acting element responsive to cold and drought, the C-repeat/dehydration-responsive element (C/DRE), was identified in the Arabidopsis thaliana stress-inducible genes RD29A and COR15a and f...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1298

    authors： Kim HJ,Hyun Y,Park JY,Park MJ,Park MK,Kim MD,Kim HJ,Lee MH,Moon J,Lee I,Kim J

    更新日期：2004-02-01 00:00:00

  • Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants.

    abstract：:An earlier search in the human, mouse and rat genomes for sequences that are 100% conserved in orthologous segments and > or = 200 bp in length identified 481 distinct sequences. These human-mouse-rat sequences, which represent ultraconserved elements (UCEs), are believed to be important for functions involving DNA bi...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1888

    authors： Derti A,Roth FP,Church GM,Wu CT

    更新日期：2006-10-01 00:00:00

  • Widespread occurrence of alternative splicing at NAGNAG acceptors contributes to proteome plasticity.

    abstract：:Splice acceptors with the genomic NAGNAG motif may cause NAG insertion-deletions in transcripts, occur in 30% of human genes and are functional in at least 5% of human genes. We found five significant biases indicating that their distribution is nonrandom and that they are evolutionarily conserved and tissue-specific....

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1469

    authors： Hiller M,Huse K,Szafranski K,Jahn N,Hampe J,Schreiber S,Backofen R,Platzer M

    更新日期：2004-12-01 00:00:00

  • A point mutation in the FMR-1 gene associated with fragile X mental retardation.

    abstract：:The vast majority of patients with fragile X syndrome show a folate-sensitive fragile site at Xq27.3 (FRAXA) at the cytogenetic level, and both amplification of the (CGG)n repeat and hypermethylation of the CpG island in the 5' fragile X gene (FMR-1) at the molecular level. We have studied the FMR-1 gene of a patient ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0193-31

    authors： De Boulle K,Verkerk AJ,Reyniers E,Vits L,Hendrickx J,Van Roy B,Van den Bos F,de Graaff E,Oostra BA,Willems PJ

    更新日期：1993-01-01 00:00:00

  • Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita).

    abstract：:Thomsen's disease (autosomal dominant myotonia congenita) has recently been linked to chromosome 7q35 in the region of the human skeletal muscle chloride channel gene (HUMCLC). Single strand conformation polymorphism analysis (SSCP) was used to screen DNA from members of four unrelated pedigrees with this disorder for...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0493-305

    authors： George AL Jr,Crackower MA,Abdalla JA,Hudson AJ,Ebers GC

    更新日期：1993-04-01 00:00:00

  • Publisher Correction: Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.

    abstract：:In the version of this article initially published, '+' and '-' labels were missing from the graph keys at the bottom of Fig. 8d. The error has been corrected in the HTML and PDF versions of the article. ...

    journal_title：Nature genetics

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41588-018-0341-3

    authors： Fanucchi S,Fok ET,Dalla E,Shibayama Y,Börner K,Chang EY,Stoychev S,Imakaev M,Grimm D,Wang KC,Li G,Sung WK,Mhlanga MM

    更新日期：2019-02-01 00:00:00

  • Genomic privacy and limits of individual detection in a pool.

    abstract：:Recent studies have demonstrated that statistical methods can be used to detect the presence of a single individual within a study group based on summary data reported from genome-wide association studies (GWAS). We present an analytical and empirical study of the statistical power of such methods. We thereby aim to p...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.436

    authors： Sankararaman S,Obozinski G,Jordan MI,Halperin E

    更新日期：2009-09-01 00:00:00

  • Genome-wide association study of PR interval.

    abstract：:The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AG...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.517

    authors： Pfeufer A,van Noord C,Marciante KD,Arking DE,Larson MG,Smith AV,Tarasov KV,Müller M,Sotoodehnia N,Sinner MF,Verwoert GC,Li M,Kao WH,Köttgen A,Coresh J,Bis JC,Psaty BM,Rice K,Rotter JI,Rivadeneira F,Hofman A,Kors

    更新日期：2010-02-01 00:00:00

  • Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

    abstract：:Uterine leiomyomata (fibroids) are common and clinically important tumors, but little is known about their etiology and pathogenesis. We previously mapped a gene that predisposes to multiple fibroids, cutaneous leiomyomata and renal cell carcinoma to chromosome 1q42.3-q43 (refs 4-6). Here we show, through a combinatio...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng849

    authors： Tomlinson IP,Alam NA,Rowan AJ,Barclay E,Jaeger EE,Kelsell D,Leigh I,Gorman P,Lamlum H,Rahman S,Roylance RR,Olpin S,Bevan S,Barker K,Hearle N,Houlston RS,Kiuru M,Lehtonen R,Karhu A,Vilkki S,Laiho P,Eklund C,Vie

    更新日期：2002-04-01 00:00:00

  • OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28.

    abstract：:Autosomal dominant optic atrophy (ADOA) is the most prevalent hereditary optic neuropathy resulting in progressive loss of visual acuity, centrocoecal scotoma and bilateral temporal atrophy of the optic nerve with an onset within the first two decades of life. The predominant locus for this disorder (OPA1; MIM 165500)...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/79944

    authors： Alexander C,Votruba M,Pesch UE,Thiselton DL,Mayer S,Moore A,Rodriguez M,Kellner U,Leo-Kottler B,Auburger G,Bhattacharya SS,Wissinger B

    更新日期：2000-10-01 00:00:00

  • Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens.

    abstract：:Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftrm1HGU mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkhold...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0495-351

    authors： Davidson DJ,Dorin JR,McLachlan G,Ranaldi V,Lamb D,Doherty C,Govan J,Porteous DJ

    更新日期：1995-04-01 00:00:00

  • Public resources aid diabetes gene discovery.

    abstract：: ...

    journal_title：Nature genetics

    pub_type： 评论,杂志文章

    doi：10.1038/s41588-018-0242-5

    authors： Cousminer DL,Grant SFA

    更新日期：2018-11-01 00:00:00

  • A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically rearranged in two primary breast cancers.

    abstract：:From chromosomal region 17q21.3, where a tumour suppressor gene(s) for breast and ovarian cancers is thought to be present, we have isolated a novel gene from a cosmid clone that revealed somatic rearrangements in two breast cancers. The gene (MDC) encodes a 524-amino acid metalloprotease-like, disintegrin-like and cy...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1093-151

    authors： Emi M,Katagiri T,Harada Y,Saito H,Inazawa J,Ito I,Kasumi F,Nakamura Y

    更新日期：1993-10-01 00:00:00

  • DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1.

    abstract：:The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human disorder, usually associated with deletions of chromosome 22q11. The genetic basis for the wide range of developmental anomalies in the heart, glands and facial structures has been elusive. We have investigated the potential role of one can...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/85845

    authors： Jerome LA,Papaioannou VE

    更新日期：2001-03-01 00:00:00

  • RAF1 mutations in childhood-onset dilated cardiomyopathy.

    abstract：:Dilated cardiomyopathy (DCM) is a highly heterogeneous trait with sarcomeric gene mutations predominating. The cause of a substantial percentage of DCMs remains unknown, and no gene-specific therapy is available. On the basis of resequencing of 513 DCM cases and 1,150 matched controls from various cohorts of distinct ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2963

    authors： Dhandapany PS,Razzaque MA,Muthusami U,Kunnoth S,Edwards JJ,Mulero-Navarro S,Riess I,Pardo S,Sheng J,Rani DS,Rani B,Govindaraj P,Flex E,Yokota T,Furutani M,Nishizawa T,Nakanishi T,Robbins J,Limongelli G,Hajjar RJ,L

    更新日期：2014-06-01 00:00:00