Different roles of eukaryotic MutS and MutL complexes in repair of small insertion and deletion loops in yeast.

Abstract:

:DNA mismatch repair greatly increases genome fidelity by recognizing and removing replication errors. In order to understand how this fidelity is maintained, it is important to uncover the relative specificities of the different components of mismatch repair. There are two major mispair recognition complexes in eukaryotes that are homologues of bacterial MutS proteins, MutSα and MutSβ, with MutSα recognizing base-base mismatches and small loop mispairs and MutSβ recognizing larger loop mispairs. Upon recognition of a mispair, the MutS complexes then interact with homologues of the bacterial MutL protein. Loops formed on the primer strand during replication lead to insertion mutations, whereas loops on the template strand lead to deletions. We show here in yeast, using oligonucleotide transformation, that MutSα has a strong bias toward repair of insertion loops, while MutSβ has an even stronger bias toward repair of deletion loops. Our results suggest that this bias in repair is due to the different interactions of the MutS complexes with the MutL complexes. Two mutants of MutLα, pms1-G882E and pms1-H888R, repair deletion mispairs but not insertion mispairs. Moreover, we find that a different MutL complex, MutLγ, is extremely important, but not sufficient, for deletion repair in the presence of either MutLα mutation. MutSβ is present in many eukaryotic organisms, but not in prokaryotes. We suggest that the biased repair of deletion mispairs may reflect a critical eukaryotic function of MutSβ in mismatch repair.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Romanova NV,Crouse GF

doi

10.1371/journal.pgen.1003920

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

e1003920

issue

10

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-13-01386

journal_volume

9

pub_type

杂志文章
  • An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans.

    abstract::A crucial step in the development of muscle cells in all metazoan animals is the assembly and anchorage of the sarcomere, the essential repeat unit responsible for muscle contraction. In Caenorhabditis elegans, many of the critical proteins involved in this process have been uncovered through mutational screens focusi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000537

    authors: Meissner B,Warner A,Wong K,Dube N,Lorch A,McKay SJ,Khattra J,Rogalski T,Somasiri A,Chaudhry I,Fox RM,Miller DM 3rd,Baillie DL,Holt RA,Jones SJ,Marra MA,Moerman DG

    更新日期:2009-06-01 00:00:00

  • Expression quantitative trait loci are highly sensitive to cellular differentiation state.

    abstract::Genetical genomics is a strategy for mapping gene expression variation to expression quantitative trait loci (eQTLs). We performed a genetical genomics experiment in four functionally distinct but developmentally closely related hematopoietic cell populations isolated from the BXD panel of recombinant inbred mouse str...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000692

    authors: Gerrits A,Li Y,Tesson BM,Bystrykh LV,Weersing E,Ausema A,Dontje B,Wang X,Breitling R,Jansen RC,de Haan G

    更新日期:2009-10-01 00:00:00

  • A trans-acting Variant within the Transcription Factor RIM101 Interacts with Genetic Background to Determine its Regulatory Capacity.

    abstract::Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005746

    authors: Read T,Richmond PA,Dowell RD

    更新日期:2016-01-11 00:00:00

  • Genome Wide Identification of SARS-CoV Susceptibility Loci Using the Collaborative Cross.

    abstract::New systems genetics approaches are needed to rapidly identify host genes and genetic networks that regulate complex disease outcomes. Using genetically diverse animals from incipient lines of the Collaborative Cross mouse panel, we demonstrate a greatly expanded range of phenotypes relative to classical mouse models ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005504

    authors: Gralinski LE,Ferris MT,Aylor DL,Whitmore AC,Green R,Frieman MB,Deming D,Menachery VD,Miller DR,Buus RJ,Bell TA,Churchill GA,Threadgill DW,Katze MG,McMillan L,Valdar W,Heise MT,Pardo-Manuel de Villena F,Baric RS

    更新日期:2015-10-09 00:00:00

  • Improved statistics for genome-wide interaction analysis.

    abstract::Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under ...

    journal_title:PLoS genetics

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pgen.1002625

    authors: Ueki M,Cordell HJ

    更新日期:2012-01-01 00:00:00

  • Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution.

    abstract::Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks (GRNs). The genes at such evolutionary 'hotspots' are thought to maximally affect the phenotype with minimal pleiotropic consequences. This has led to the suggestion that if a GRN is unde...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007375

    authors: Kittelmann S,Buffry AD,Franke FA,Almudi I,Yoth M,Sabaris G,Couso JP,Nunes MDS,Frankel N,Gómez-Skarmeta JL,Pueyo-Marques J,Arif S,McGregor AP

    更新日期:2018-05-03 00:00:00

  • Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack.

    abstract::UV-induced DNA damage causes repression of RNA synthesis. Following the removal of DNA lesions, transcription recovery operates through a process that is not understood yet. Here we show that knocking-out of the histone methyltransferase DOT1L in mouse embryonic fibroblasts (MEF(DOT1L)) leads to a UV hypersensitivity ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003611

    authors: Oksenych V,Zhovmer A,Ziani S,Mari PO,Eberova J,Nardo T,Stefanini M,Giglia-Mari G,Egly JM,Coin F

    更新日期:2013-01-01 00:00:00

  • Genetic mapping of MAPK-mediated complex traits Across S. cerevisiae.

    abstract::Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004913

    authors: Treusch S,Albert FW,Bloom JS,Kotenko IE,Kruglyak L

    更新日期:2015-01-08 00:00:00

  • Ku Binding on Telomeres Occurs at Sites Distal from the Physical Chromosome Ends.

    abstract::The Ku complex binds non-specifically to DNA breaks and ensures repair via NHEJ. However, Ku is also known to bind directly to telomeric DNA ends and its presence there is associated with telomere capping, but avoiding NHEJ. How the complex discriminates between a DNA break and a telomeric extremity remains unknown. O...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006479

    authors: Larcher MV,Pasquier E,MacDonald RS,Wellinger RJ

    更新日期:2016-12-08 00:00:00

  • Recovery of novel association loci in Arabidopsis thaliana and Drosophila melanogaster through leveraging INDELs association and integrated burden test.

    abstract::Short insertions, deletions (INDELs) and larger structural variants have been increasingly employed in genetic association studies, but few improvements over SNP-based association have been reported. In order to understand why this might be the case, we analysed two publicly available datasets and observed that 63% of...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007699

    authors: Song B,Mott R,Gan X

    更新日期:2018-10-16 00:00:00

  • Proofreading activity of DNA polymerase Pol2 mediates 3'-end processing during nonhomologous end joining in yeast.

    abstract::Genotoxic agents that cause double-strand breaks (DSBs) often generate damage at the break termini. Processing enzymes, including nucleases and polymerases, must remove damaged bases and/or add new bases before completion of repair. Artemis is a nuclease involved in mammalian nonhomologous end joining (NHEJ), but in S...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000060

    authors: Tseng SF,Gabriel A,Teng SC

    更新日期:2008-04-25 00:00:00

  • Allele-specific virulence attenuation of the Pseudomonas syringae HopZ1a type III effector via the Arabidopsis ZAR1 resistance protein.

    abstract::Plant resistance (R) proteins provide a robust surveillance system to defend against potential pathogens. Despite their importance in plant innate immunity, relatively few of the approximately 170 R proteins in Arabidopsis have well-characterized resistance specificity. In order to identify the R protein responsible f...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000894

    authors: Lewis JD,Wu R,Guttman DS,Desveaux D

    更新日期:2010-04-01 00:00:00

  • WDR23 regulates NRF2 independently of KEAP1.

    abstract::Cellular adaptation to stress is essential to ensure organismal survival. NRF2/NFE2L2 is a key determinant of xenobiotic stress responses, and loss of negative regulation by the KEAP1-CUL3 proteasome system is implicated in several chemo- and radiation-resistant cancers. Advantageously using C. elegans alongside human...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006762

    authors: Lo JY,Spatola BN,Curran SP

    更新日期:2017-04-28 00:00:00

  • The pivotal roles of TIA proteins in 5' splice-site selection of alu exons and across evolution.

    abstract::More than 5% of alternatively spliced internal exons in the human genome are derived from Alu elements in a process termed exonization. Alus are comprised of two homologous arms separated by an internal polypyrimidine tract (PPT). In most exonizations, splice sites are selected from within the same arm. We hypothesize...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000717

    authors: Gal-Mark N,Schwartz S,Ram O,Eyras E,Ast G

    更新日期:2009-11-01 00:00:00

  • Evolution of the Auxin Response Factors from charophyte ancestors.

    abstract::Auxin is a major developmental regulator in plants and the acquisition of a transcriptional response to auxin likely contributed to developmental innovations at the time of water-to-land transition. Auxin Response Factors (ARFs) Transcription Factors (TFs) that mediate auxin-dependent transcriptional changes are divid...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008400

    authors: Martin-Arevalillo R,Thévenon E,Jégu F,Vinos-Poyo T,Vernoux T,Parcy F,Dumas R

    更新日期:2019-09-25 00:00:00

  • Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.

    abstract::In mammalian meiosis, homologous chromosome synapsis is coupled with recombination. As in most eukaryotes, mammalian meiocytes have checkpoints that monitor the fidelity of these processes. We report that the mouse ortholog (Trip13) of pachytene checkpoint 2 (PCH2), an essential component of the synapsis checkpoint in...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030130

    authors: Li XC,Schimenti JC

    更新日期:2007-08-01 00:00:00

  • Transcription facilitated genome-wide recruitment of topoisomerase I and DNA gyrase.

    abstract::Movement of the transcription machinery along a template alters DNA topology resulting in the accumulation of supercoils in DNA. The positive supercoils generated ahead of transcribing RNA polymerase (RNAP) and the negative supercoils accumulating behind impose severe topological constraints impeding transcription pro...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006754

    authors: Ahmed W,Sala C,Hegde SR,Jha RK,Cole ST,Nagaraja V

    更新日期:2017-05-02 00:00:00

  • Identification of a novel type of spacer element required for imprinting in fission yeast.

    abstract::Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal imprint. This imprint has been shown to consist of two ribonucleotides ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001328

    authors: Sayrac S,Vengrova S,Godfrey EL,Dalgaard JZ

    更新日期:2011-03-01 00:00:00

  • Integrating multiple genomic data to predict disease-causing nonsynonymous single nucleotide variants in exome sequencing studies.

    abstract::Exome sequencing has been widely used in detecting pathogenic nonsynonymous single nucleotide variants (SNVs) for human inherited diseases. However, traditional statistical genetics methods are ineffective in analyzing exome sequencing data, due to such facts as the large number of sequenced variants, the presence of ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004237

    authors: Wu J,Li Y,Jiang R

    更新日期:2014-03-20 00:00:00

  • Pathways of distinction analysis: a new technique for multi-SNP analysis of GWAS data.

    abstract::Genome-wide association studies (GWAS) have become increasingly common due to advances in technology and have permitted the identification of differences in single nucleotide polymorphism (SNP) alleles that are associated with diseases. However, while typical GWAS analysis techniques treat markers individually, comple...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002101

    authors: Braun R,Buetow K

    更新日期:2011-06-01 00:00:00

  • Transcriptional dynamics elicited by a short pulse of notch activation involves feed-forward regulation by E(spl)/Hes genes.

    abstract::Dynamic activity of signaling pathways, such as Notch, is vital to achieve correct development and homeostasis. However, most studies assess output many hours or days after initiation of signaling, once the outcome has been consolidated. Here we analyze genome-wide changes in transcript levels, binding of the Notch pa...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003162

    authors: Housden BE,Fu AQ,Krejci A,Bernard F,Fischer B,Tavaré S,Russell S,Bray SJ

    更新日期:2013-01-01 00:00:00

  • Identification of the master sex determining gene in Northern pike (Esox lucius) reveals restricted sex chromosome differentiation.

    abstract::Teleost fishes, thanks to their rapid evolution of sex determination mechanisms, provide remarkable opportunities to study the formation of sex chromosomes and the mechanisms driving the birth of new master sex determining (MSD) genes. However, the evolutionary interplay between the sex chromosomes and the MSD genes t...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008013

    authors: Pan Q,Feron R,Yano A,Guyomard R,Jouanno E,Vigouroux E,Wen M,Busnel JM,Bobe J,Concordet JP,Parrinello H,Journot L,Klopp C,Lluch J,Roques C,Postlethwait J,Schartl M,Herpin A,Guiguen Y

    更新日期:2019-08-22 00:00:00

  • The amidation step of diphthamide biosynthesis in yeast requires DPH6, a gene identified through mining the DPH1-DPH5 interaction network.

    abstract::Diphthamide is a highly modified histidine residue in eukaryal translation elongation factor 2 (eEF2) that is the target for irreversible ADP ribosylation by diphtheria toxin (DT). In Saccharomyces cerevisiae, the initial steps of diphthamide biosynthesis are well characterized and require the DPH1-DPH5 genes. However...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003334

    authors: Uthman S,Bär C,Scheidt V,Liu S,ten Have S,Giorgini F,Stark MJ,Schaffrath R

    更新日期:2013-01-01 00:00:00

  • The small GTPase RAB-35 defines a third pathway that is required for the recognition and degradation of apoptotic cells.

    abstract::In metazoans, apoptotic cells are swiftly engulfed by phagocytes and degraded inside phagosomes. Multiple small GTPases in the Rab family are known to function in phagosome maturation by regulating vesicle trafficking. We discovered rab-35 as a new gene important for apoptotic cell clearance from a genetic screen targ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007558

    authors: Haley R,Wang Y,Zhou Z

    更新日期:2018-08-23 00:00:00

  • Loss of the Caenorhabditis elegans pocket protein LIN-35 reveals MuvB's innate function as the repressor of DREAM target genes.

    abstract::The DREAM (Dp/Retinoblastoma(Rb)-like/E2F/MuvB) transcriptional repressor complex acts as a gatekeeper of the mammalian cell cycle by establishing and maintaining cellular quiescence. How DREAM's three functional components, the E2F-DP heterodimer, the Rb-like pocket protein, and the MuvB subcomplex, form and function...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007088

    authors: Goetsch PD,Garrigues JM,Strome S

    更新日期:2017-11-01 00:00:00

  • A germline polymorphism of thymine DNA glycosylase induces genomic instability and cellular transformation.

    abstract::Thymine DNA glycosylase (TDG) functions in base excision repair, a DNA repair pathway that acts in a lesion-specific manner to correct individual damaged or altered bases. TDG preferentially catalyzes the removal of thymine and uracil paired with guanine, and is also active on 5-fluorouracil (5-FU) paired with adenine...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004753

    authors: Sjolund A,Nemec AA,Paquet N,Prakash A,Sung P,Doublié S,Sweasy JB

    更新日期:2014-11-06 00:00:00

  • A Cyclin A-Myb-MuvB-Aurora B network regulates the choice between mitotic cycles and polyploid endoreplication cycles.

    abstract::Endoreplication is a cell cycle variant that entails cell growth and periodic genome duplication without cell division, and results in large, polyploid cells. Cells switch from mitotic cycles to endoreplication cycles during development, and also in response to conditional stimuli during wound healing, regeneration, a...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008253

    authors: Rotelli MD,Policastro RA,Bolling AM,Killion AW,Weinberg AJ,Dixon MJ,Zentner GE,Walczak CE,Lilly MA,Calvi BR

    更新日期:2019-07-10 00:00:00

  • Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.

    abstract::Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants t...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002013

    authors: Murphy JT,Bruinsma JJ,Schneider DL,Collier S,Guthrie J,Chinwalla A,Robertson JD,Mardis ER,Kornfeld K

    更新日期:2011-03-01 00:00:00

  • Biased, non-equivalent gene-proximal and -distal binding motifs of orphan nuclear receptor TR4 in primary human erythroid cells.

    abstract::We previously reported that TR2 and TR4 orphan nuclear receptors bind to direct repeat (DR) elements in the ε- and γ-globin promoters, and act as molecular anchors for the recruitment of epigenetic corepressors of the multifaceted DRED complex, thereby leading to ε- and γ-globin transcriptional repression during defin...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004339

    authors: Shi L,Sierant MC,Gurdziel K,Zhu F,Cui S,Kolodziej KE,Strouboulis J,Guan Y,Tanabe O,Lim KC,Engel JD

    更新日期:2014-05-08 00:00:00

  • Systematic dissection of coding exons at single nucleotide resolution supports an additional role in cell-specific transcriptional regulation.

    abstract::In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004592

    authors: Birnbaum RY,Patwardhan RP,Kim MJ,Findlay GM,Martin B,Zhao J,Bell RJ,Smith RP,Ku AA,Shendure J,Ahituv N

    更新日期:2014-10-23 00:00:00