Incision-dependent and error-free repair of (CAG)(n)/(CTG)(n) hairpins in human cell extracts.

Abstract:

:Expansion of CAG/CTG trinucleotide repeats is associated with certain familial neurological disorders, including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism contributes to their expansion. However, the molecular mechanism(s) by which cells remove CAG/CTG hairpins remain unknown. Here we demonstrate that human cell extracts can catalyze error-free repair of CAG/CTG hairpins in a nick-directed manner. The repair system specifically targets CAG/CTG tracts for incisions in the nicked DNA strand, followed by DNA resynthesis using the continuous strand as a template, thereby ensuring CAG/CTG stability. Proliferating cell nuclear antigen (PCNA) is required for the incision step of the hairpin removal, which uses distinct endonuclease activities for individual CAG/CTG hairpins depending on their strand locations and/or secondary structures. We discuss the implications of these data for understanding the etiology of neurological diseases and trinucleotide repeat instability.

journal_name

Nat Struct Mol Biol

authors

Hou C,Chan NL,Gu L,Li GM

doi

10.1038/nsmb.1638

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

869-75

issue

8

eissn

1545-9993

issn

1545-9985

pii

nsmb.1638

journal_volume

16

pub_type

杂志文章
  • RNA secondary structure in mutually exclusive splicing.

    abstract::Mutually exclusive splicing is a regulated means to generate protein diversity, but the underlying mechanisms are poorly understood. Here comparative genome analysis revealed the built-in intronic elements for controlling mutually exclusive splicing of the 14-3-3ξ pre-mRNA. These elements are clade specific but are ev...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1959

    authors: Yang Y,Zhan L,Zhang W,Sun F,Wang W,Tian N,Bi J,Wang H,Shi D,Jiang Y,Zhang Y,Jin Y

    更新日期:2011-02-01 00:00:00

  • Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer.

    abstract::Long noncoding RNAs (lncRNAs) play critical roles during tumorigenesis by functioning as scaffolds that regulate protein-protein, protein-DNA or protein-RNA interactions. Using a clinically guided genetic screening approach, we identified lncRNA in nonhomologous end joining (NHEJ) pathway 1 (LINP1), which is overexpre...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3211

    authors: Zhang Y,He Q,Hu Z,Feng Y,Fan L,Tang Z,Yuan J,Shan W,Li C,Hu X,Tanyi JL,Fan Y,Huang Q,Montone K,Dang CV,Zhang L

    更新日期:2016-06-01 00:00:00

  • Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome.

    abstract::SIX1 interacts with EYA to form a bipartite transcription factor essential for mammalian development. Loss of function of this complex causes branchio-oto-renal (BOR) syndrome, whereas re-expression of SIX1 or EYA promotes metastasis. Here we describe the 2.0-Å structure of SIX1 bound to EYA2, which suggests a new DNA...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2505

    authors: Patrick AN,Cabrera JH,Smith AL,Chen XS,Ford HL,Zhao R

    更新日期:2013-04-01 00:00:00

  • Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses.

    abstract::The association of Zika virus (ZIKV) infections with microcephaly has resulted in an ongoing public-health emergency. Here we report the crystal structure of a C-terminal fragment of ZIKV nonstructural protein 1 (NS1), a major host-interaction molecule that functions in flaviviral replication, pathogenesis and immune ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3213

    authors: Song H,Qi J,Haywood J,Shi Y,Gao GF

    更新日期:2016-05-01 00:00:00

  • Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.

    abstract::The PHD finger protein 1 (PHF1) is essential in epigenetic regulation and genome maintenance. Here we show that the Tudor domain of human PHF1 binds to histone H3 trimethylated at Lys36 (H3K36me3). We report a 1.9-Å resolution crystal structure of the Tudor domain in complex with H3K36me3 and describe the molecular me...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2435

    authors: Musselman CA,Avvakumov N,Watanabe R,Abraham CG,Lalonde ME,Hong Z,Allen C,Roy S,Nuñez JK,Nickoloff J,Kulesza CA,Yasui A,Côté J,Kutateladze TG

    更新日期:2012-12-01 00:00:00

  • T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease.

    abstract::Celiac disease is a T cell-mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epi...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2817

    authors: Petersen J,Montserrat V,Mujico JR,Loh KL,Beringer DX,van Lummel M,Thompson A,Mearin ML,Schweizer J,Kooy-Winkelaar Y,van Bergen J,Drijfhout JW,Kan WT,La Gruta NL,Anderson RP,Reid HH,Koning F,Rossjohn J

    更新日期:2014-05-01 00:00:00

  • The SM protein Vps33 and the t-SNARE H(abc) domain promote fusion pore opening.

    abstract::Intracellular membrane fusion proceeds via distinct stages of membrane docking, hemifusion and fusion pore opening and depends on interacting families of Rab, SNARE and SM proteins. Trans-SNARE complexes dock the membranes in close apposition. Efficient fusion requires further SNARE-associated proteins. They might inc...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1809

    authors: Pieren M,Schmidt A,Mayer A

    更新日期:2010-06-01 00:00:00

  • USP7 is a SUMO deubiquitinase essential for DNA replication.

    abstract::Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3185

    authors: Lecona E,Rodriguez-Acebes S,Specks J,Lopez-Contreras AJ,Ruppen I,Murga M,Muñoz J,Mendez J,Fernandez-Capetillo O

    更新日期:2016-04-01 00:00:00

  • ATP-dependent chromatin remodeling shapes the DNA replication landscape.

    abstract::The eukaryotic DNA replication machinery must traverse every nucleosome in the genome during S phase. As nucleosomes are generally inhibitory to DNA-dependent processes, chromatin structure must undergo extensive reorganization to facilitate DNA synthesis. However, the identity of chromatin-remodeling factors involved...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1419

    authors: Vincent JA,Kwong TJ,Tsukiyama T

    更新日期:2008-05-01 00:00:00

  • Ligands bind to Sortilin in the tunnel of a ten-bladed beta-propeller domain.

    abstract::The structure of the Sortilin ectodomain in complex with neurotensin has been determined at 2-A resolution, revealing that the C-terminal part of neurotensin binds in the tunnel of a ten-bladed beta-propeller domain. Binding competition studies suggest that additional binding sites, for example, for the prodomain of n...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1543

    authors: Quistgaard EM,Madsen P,Grøftehauge MK,Nissen P,Petersen CM,Thirup SS

    更新日期:2009-01-01 00:00:00

  • Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2.

    abstract::Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 methylation patterns remain incompletely understood. Epigenetic mechanism...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-018-0036-6

    authors: Højfeldt JW,Laugesen A,Willumsen BM,Damhofer H,Hedehus L,Tvardovskiy A,Mohammad F,Jensen ON,Helin K

    更新日期:2018-03-01 00:00:00

  • Structural basis for mRNA recognition by elongation factor SelB.

    abstract::In bacteria, incorporation of selenocysteine, the 21(st) amino acid, into proteins requires elongation factor SelB, which has the unusual property of binding to both transfer RNA (tRNA) and mRNA. SelB binds to an mRNA hairpin formed by the selenocysteine insertion sequence (SECIS) with extremely high specificity, the ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb890

    authors: Yoshizawa S,Rasubala L,Ose T,Kohda D,Fourmy D,Maenaka K

    更新日期:2005-02-01 00:00:00

  • The hunt for RNA polymerase II elongation factors: a historical perspective.

    abstract::The discovery of the three eukaryotic nuclear RNA polymerases paved the way for serious biochemical investigations of eukaryotic transcription and the identification of eukaryotic transcription factors. Here we describe this adventure from our vantage point, with a focus on the hunt for factors that regulate elongatio...

    journal_title:Nature structural & molecular biology

    pub_type: 历史文章,杂志文章,评审

    doi:10.1038/s41594-019-0283-1

    authors: Conaway RC,Conaway JW

    更新日期:2019-09-01 00:00:00

  • An assessment of histone-modification antibody quality.

    abstract::We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibo...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1972

    authors: Egelhofer TA,Minoda A,Klugman S,Lee K,Kolasinska-Zwierz P,Alekseyenko AA,Cheung MS,Day DS,Gadel S,Gorchakov AA,Gu T,Kharchenko PV,Kuan S,Latorre I,Linder-Basso D,Luu Y,Ngo Q,Perry M,Rechtsteiner A,Riddle NC,Schwar

    更新日期:2011-01-01 00:00:00

  • Notch is a direct negative regulator of the DNA-damage response.

    abstract::The DNA-damage response (DDR) ensures genome stability and proper inheritance of genetic information, both of which are essential to survival. It is presently unclear to what extent other signaling pathways modulate DDR function. Here we show that Notch receptor binds and inactivates ATM kinase and that this mechanism...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3013

    authors: Vermezovic J,Adamowicz M,Santarpia L,Rustighi A,Forcato M,Lucano C,Massimiliano L,Costanzo V,Bicciato S,Del Sal G,d'Adda di Fagagna F

    更新日期:2015-05-01 00:00:00

  • Octaheme tetrathionate reductase is a respiratory enzyme with novel heme ligation.

    abstract::We have isolated a soluble cytochrome from Shewanella oneidensis that contains eight covalently attached heme groups and determined its crystal structure. One of these hemes exhibits novel ligation of the iron atom by the epsilon-amino group of a lysine residue, despite its attachment via a typical CXXCH motif. This h...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb827

    authors: Mowat CG,Rothery E,Miles CS,McIver L,Doherty MK,Drewette K,Taylor P,Walkinshaw MD,Chapman SK,Reid GA

    更新日期:2004-10-01 00:00:00

  • The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity.

    abstract::In voltage-gated sodium, potassium and calcium channels, the functions of ion conduction and voltage sensing are performed by two distinct structural units: the pore domain and the voltage-sensing domain (VSD). In the hydrogen voltage-gated channel 1 (Hv1), the VSD, unusually, performs both functions. Hv1 was recently...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1738

    authors: Tombola F,Ulbrich MH,Kohout SC,Isacoff EY

    更新日期:2010-01-01 00:00:00

  • Quantification of translation uncovers the functions of the alternative transcriptome.

    abstract::Translation has a fundamental function in defining the fate of the transcribed genome. RNA-sequencing (RNA-seq) data enable the quantification of complex transcript mixtures, often detecting several transcript isoforms of unknown functions for one gene. Here, we describe ORFquant, a method to annotate and quantify tra...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-020-0450-4

    authors: Calviello L,Hirsekorn A,Ohler U

    更新日期:2020-08-01 00:00:00

  • Structure of an aprataxin-DNA complex with insights into AOA1 neurodegenerative disease.

    abstract::DNA ligases finalize DNA replication and repair through DNA nick-sealing reactions that can abort to generate cytotoxic 5'-adenylation DNA damage. Aprataxin (Aptx) catalyzes direct reversal of 5'-adenylate adducts to protect genome integrity. Here the structure of a Schizosaccharomyces pombe Aptx-DNA-AMP-Zn(2+) comple...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2146

    authors: Tumbale P,Appel CD,Kraehenbuehl R,Robertson PD,Williams JS,Krahn J,Ahel I,Williams RS

    更新日期:2011-10-09 00:00:00

  • Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome.

    abstract::The polypyrimidine tract binding protein (PTB) binds pre-mRNAs to alter splice-site choice. We characterized a series of spliceosomal complexes that assemble on a pre-mRNA under conditions of either PTB-mediated splicing repression or its absence. In the absence of repression, exon definition complexes that were assem...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.1375

    authors: Sharma S,Kohlstaedt LA,Damianov A,Rio DC,Black DL

    更新日期:2008-02-01 00:00:00

  • A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators.

    abstract::Glucokinase (GK) is a glucose-phosphorylating enzyme that regulates insulin release and hepatic metabolism, and its loss of function is implicated in diabetes pathogenesis. GK activators (GKAs) are attractive therapeutics in diabetes; however, clinical data indicate that their benefits can be offset by hypoglycemia, o...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2717

    authors: Szlyk B,Braun CR,Ljubicic S,Patton E,Bird GH,Osundiji MA,Matschinsky FM,Walensky LD,Danial NN

    更新日期:2014-01-01 00:00:00

  • RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20.

    abstract::Previous studies have linked the C-terminal domain (CTD) of RNA polymerase II (pol II) with cotranscriptional precursor messenger RNA processing, but little is known about the CTD's function in regulating alternative splicing. We have examined this function using alpha-amanitin-resistant pol II CTD mutants and fibrone...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1155

    authors: de la Mata M,Kornblihtt AR

    更新日期:2006-11-01 00:00:00

  • A popular engagement at the ends.

    abstract::Three recent studies converged on a specific protein-protein interface between TPP1 and telomerase as being crucial for the regulation of both telomerase recruitment and processivity in mammalian cells. An equivalent interaction appears to exist in budding yeast, making this a nearly universal means of telomerase regu...

    journal_title:Nature structural & molecular biology

    pub_type: 新闻

    doi:10.1038/nsmb.2483

    authors: Lue NF,Yu EY,Lei M

    更新日期:2013-01-01 00:00:00

  • Xist-dependent imprinted X inactivation and the early developmental consequences of its failure.

    abstract::The long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryo...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.3365

    authors: Borensztein M,Syx L,Ancelin K,Diabangouaya P,Picard C,Liu T,Liang JB,Vassilev I,Galupa R,Servant N,Barillot E,Surani A,Chen CJ,Heard E

    更新日期:2017-03-01 00:00:00

  • Reconstitution of anaphase DNA bridge recognition and disjunction.

    abstract::Faithful chromosome segregation requires that the sister chromatids be disjoined completely. Defective disjunction can lead to the persistence of histone-free threads of DNA known as ultra-fine bridges (UFBs) that connect the separating sister DNA molecules during anaphase. UFBs arise at specific genomic loci and can ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/s41594-018-0123-8

    authors: Sarlós K,Biebricher AS,Bizard AH,Bakx JAM,Ferreté-Bonastre AG,Modesti M,Paramasivam M,Yao Q,Peterman EJG,Wuite GJL,Hickson ID

    更新日期:2018-09-01 00:00:00

  • MRE11-RAD50-NBS1 and ATM function as co-mediators of TRF1 in telomere length control.

    abstract::Human telomeres are associated with ATM and the protein complex consisting of MRE11, RAD50 and NBS1 (MRN), which are central to maintaining genomic stability. Here we show that when targeted to telomeres, wild-type RAD50 downregulates telomeric association of TRF1, a negative regulator of telomere maintenance. TRF1 bi...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1286

    authors: Wu Y,Xiao S,Zhu XD

    更新日期:2007-09-01 00:00:00

  • Recognition of helical kinks by xeroderma pigmentosum group A protein triggers DNA excision repair.

    abstract::The function of human XPA protein, a key subunit of the nucleotide excision repair pathway, has been examined with site-directed substitutions in its putative DNA-binding cleft. After screening for repair activity in a host-cell reactivation assay, we analyzed mutants by comparing their affinities for different substr...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1061

    authors: Camenisch U,Dip R,Schumacher SB,Schuler B,Naegeli H

    更新日期:2006-03-01 00:00:00

  • Let K-Ras activate its own inhibitor.

    abstract:: ...

    journal_title:Nature structural & molecular biology

    pub_type: 新闻

    doi:10.1038/s41594-018-0066-0

    authors: Statsyuk AV

    更新日期:2018-06-01 00:00:00

  • Regulation of MLL1 H3K4 methyltransferase activity by its core components.

    abstract::Histone H3 Lys4 (H3K4) methylation is a prevalent mark associated with transcription activation. A common feature of several H3K4 methyltransferase complexes is the presence of three structural components (RbBP5, Ash2L and WDR5) and a catalytic subunit containing a SET domain. Here we report the first biochemical reco...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb1128

    authors: Dou Y,Milne TA,Ruthenburg AJ,Lee S,Lee JW,Verdine GL,Allis CD,Roeder RG

    更新日期:2006-08-01 00:00:00

  • Scratching the (lateral) surface of chromatin regulation by histone modifications.

    abstract::Histones have two structurally and functionally distinct domains: globular domains forming the nucleosomal core around which DNA is wrapped and unstructured tails protruding from the nucleosomal core. Whereas post-translational modifications (PTMs) in histone tails are well studied, much less is currently known about ...

    journal_title:Nature structural & molecular biology

    pub_type: 杂志文章

    doi:10.1038/nsmb.2581

    authors: Tropberger P,Schneider R

    更新日期:2013-06-01 00:00:00