A fine-scale dissection of the DNA double-strand break repair machinery and its implications for breast cancer therapy.

Abstract:

:DNA-damage response machinery is crucial to maintain the genomic integrity of cells, by enabling effective repair of even highly lethal lesions such as DNA double-strand breaks (DSBs). Defects in specific genes acquired through mutations, copy-number alterations or epigenetic changes can alter the balance of these pathways, triggering cancerous potential in cells. Selective killing of cancer cells by sensitizing them to further DNA damage, especially by induction of DSBs, therefore requires careful modulation of DSB-repair pathways. Here, we review the latest knowledge on the two DSB-repair pathways, homologous recombination and non-homologous end joining in human, describing in detail the functions of their components and the key mechanisms contributing to the repair. Such an in-depth characterization of these pathways enables a more mechanistic understanding of how cells respond to therapies, and suggests molecules and processes that can be explored as potential therapeutic targets. One such avenue that has shown immense promise is via the exploitation of synthetic lethal relationships, for which the BRCA1-PARP1 relationship is particularly notable. Here, we describe how this relationship functions and the manner in which cancer cells acquire therapy resistance by restoring their DSB repair potential.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Liu C,Srihari S,Cao KA,Chenevix-Trench G,Simpson PT,Ragan MA,Khanna KK

doi

10.1093/nar/gku284

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

6106-27

issue

10

eissn

0305-1048

issn

1362-4962

pii

gku284

journal_volume

42

pub_type

杂志文章,评审
  • Role of Era in assembly and homeostasis of the ribosomal small subunit.

    abstract::Assembly factors provide speed and directionality to the maturation process of the 30S subunit in bacteria. To gain a more precise understanding of how these proteins mediate 30S maturation, it is important to expand on studies of 30S assembly intermediates purified from bacterial strains lacking particular maturation...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz571

    authors: Razi A,Davis JH,Hao Y,Jahagirdar D,Thurlow B,Basu K,Jain N,Gomez-Blanco J,Britton RA,Vargas J,Guarné A,Woodson SA,Williamson JR,Ortega J

    更新日期:2019-09-05 00:00:00

  • Recognition of prokaryotic promoters based on a novel variable-window Z-curve method.

    abstract::Transcription is the first step in gene expression, and it is the step at which most of the regulation of expression occurs. Although sequenced prokaryotic genomes provide a wealth of information, transcriptional regulatory networks are still poorly understood using the available genomic information, largely because a...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr795

    authors: Song K

    更新日期:2012-02-01 00:00:00

  • Transcriptional and post-transcriptional regulation of storage protein gene expression in sulfur-deficient pea seeds.

    abstract::We have used in vitro transcription in isolated pea nuclei to determine whether the expression of genes for the seed storage proteins legumin and vicilin is regulated transcriptionally or post-transcriptionally in response to changing sulfur status in the developing seed. During the first 48 h of recovery from S defic...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/13.3.999

    authors: Beach LR,Spencer D,Randall PJ,Higgins TJ

    更新日期:1985-02-11 00:00:00

  • TORQUE: topology-free querying of protein interaction networks.

    abstract::TORQUE is a tool for cross-species querying of protein-protein interaction networks. It aims to answer the following question: given a set of proteins constituting a known complex or a pathway in one species, can a similar complex or pathway be found in the protein network of another species? To this end, Torque seeks...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp474

    authors: Bruckner S,Hüffner F,Karp RM,Shamir R,Sharan R

    更新日期:2009-07-01 00:00:00

  • Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.

    abstract::Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (I...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx464

    authors: Lu XM,Batugedara G,Lee M,Prudhomme J,Bunnik EM,Le Roch KG

    更新日期:2017-07-27 00:00:00

  • Higher-order structure of bovine mitochondrial tRNA(Phe) lacking the 'conserved' GG and T psi CG sequences as inferred by enzymatic and chemical probing.

    abstract::Bovine mitochondrial (mt) phenylalanine tRNA (tRNA(Phe)), which lacks the 'conserved' GG and T psi YCG sequences, was efficiently purified by the selective hybridization method using a solid phase DNA probe. The entire nucleotide sequence of the tRNA, including modified nucleotides, was determined and its higher-order...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/22.3.347

    authors: Wakita K,Watanabe Y,Yokogawa T,Kumazawa Y,Nakamura S,Ueda T,Watanabe K,Nishikawa K

    更新日期:1994-02-11 00:00:00

  • The nuclear 5S RNAs from chicken, rat and man. U5 RNAs are encoded by multiple genes.

    abstract::Preparations of chicken, rat and human nuclear 5S RNA contain two sets of molecules. The set with the lowest electrophoretic mobility (5Sa) contains RNAs identical or closely related to ribosomal 5S RNA from the corresponding animal species. In HeLa cells and rat brain, we only detected an RNA identical to the ribosom...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/9.4.769

    authors: Krol A,Gallinaro H,Lazar E,Jacob M,Branlant C

    更新日期:1981-02-25 00:00:00

  • An integrated, structure- and energy-based view of the genetic code.

    abstract::The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of no...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,评审

    doi:10.1093/nar/gkw608

    authors: Grosjean H,Westhof E

    更新日期:2016-09-30 00:00:00

  • Efficient and risk-reduced genome editing using double nicks enhanced by bacterial recombination factors in multiple species.

    abstract::Site-specific DNA double-strand breaks have been used to generate knock-in through the homology-dependent or -independent pathway. However, low efficiency and accompanying negative impacts such as undesirable indels or tumorigenic potential remain problematic. In this study, we present an enhanced reduced-risk genome ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa195

    authors: He X,Chen W,Liu Z,Yu G,Chen Y,Cai YJ,Sun L,Xu W,Zhong L,Gao C,Chen J,Zhang M,Yang S,Yao Y,Zhang Z,Ma F,Zhang CC,Lu HP,Yu B,Cheng TL,Qiu J,Sheng Q,Zhou HM,Lv ZR,Yan J,Zhou Y,Qiu Z,Cui Z,Zhang X,Me

    更新日期:2020-06-04 00:00:00

  • Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei.

    abstract::KU is a heterodimer, consisting of approximately 70 and approximately 80 kDa subunits (KU70 and KU80, respectively), which is involved in a variety of nuclear functions. We generated tbKU80-deficient trypanosomes to explore the potential role of the tbKU complex in telomere maintenance and transcriptional regulation o...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh991

    authors: Janzen CJ,Lander F,Dreesen O,Cross GA

    更新日期:2004-12-15 00:00:00

  • DNA multiplex hybridization on microarrays and thermodynamic stability in solution: a direct comparison.

    abstract::Hybridization intensities of 30 distinct short duplex DNAs measured on spotted microarrays, were directly compared with thermodynamic stabilities measured in solution. DNA sequences were designed to promote formation of perfect match, or hybrid duplexes containing tandem mismatches. Thermodynamic parameters DeltaH deg...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm865

    authors: Fish DJ,Horne MT,Brewood GP,Goodarzi JP,Alemayehu S,Bhandiwad A,Searles RP,Benight AS

    更新日期:2007-01-01 00:00:00

  • 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event.

    abstract::We describe the synthesis of 2'-O-methyl, 2'-O-ethyl oligoribonucleotides and phosphorothioate oligodeoxyribonucleotides and demonstrate their utility as inhibitors of the in vitro U7 snRNP-dependent mRNA processing event. These 2'-O-modified compounds were designed to possess the binding affinity of an RNA molecule t...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.10.2629

    authors: Cotten M,Oberhauser B,Brunar H,Holzner A,Issakides G,Noe CR,Schaffner G,Wagner E,Birnstiel ML

    更新日期:1991-05-25 00:00:00

  • Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1.

    abstract::DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential mod...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw183

    authors: Xu X,Lin A,Zhou C,Blackwell SR,Zhang Y,Wang Z,Feng Q,Guan R,Hanna MD,Chen Z,Xiao W

    更新日期:2016-06-20 00:00:00

  • Human Rad51 filaments on double- and single-stranded DNA: correlating regular and irregular forms with recombination function.

    abstract::Recombinase proteins assembled into helical filaments on DNA are believed to be the catalytic core of homologous recombination. The assembly, disassembly and dynamic rearrangements of this structure must drive the DNA strand exchange reactions of homologous recombination. The sensitivity of eukaryotic recombinase acti...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki640

    authors: Ristic D,Modesti M,van der Heijden T,van Noort J,Dekker C,Kanaar R,Wyman C

    更新日期:2005-06-08 00:00:00

  • Air2p is critical for the assembly and RNA-binding of the TRAMP complex and the KOW domain of Mtr4p is crucial for exosome activation.

    abstract::Trf4/5p-Air1/2p-Mtr4p polyadenylation complex (TRAMP) is an essential component of nuclear RNA surveillance in yeast. It recognizes a variety of nuclear transcripts produced by all three RNA polymerases, adds short poly(A) tails to aberrant or unstable RNAs and activates the exosome for their degradation. Despite the ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks223

    authors: Holub P,Lalakova J,Cerna H,Pasulka J,Sarazova M,Hrazdilova K,Arce MS,Hobor F,Stefl R,Vanacova S

    更新日期:2012-07-01 00:00:00

  • Characterization of multiple alternative RNAs resulting from antisense transcription of the PR264/SC35 splicing factor gene.

    abstract::The PR264/SC35 splicing factor belongs to the family of SR proteins which function as essential and alternative splicing factors. Here, we report that the human PR264/SC35 locus is bidirectionally transcribed. Double in situ hybridization experiments have allowed simultaneous detection of sense and antisense RNA in hu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.22.4513

    authors: Sureau A,Soret J,Guyon C,Gaillard C,Dumon S,Keller M,Crisanti P,Perbal B

    更新日期:1997-11-15 00:00:00

  • 5' flanking sequence and genomic structure of Egr-1, a murine mitogen inducible zinc finger encoding gene.

    abstract::Egr-1 is a murine zinc finger encoding cDNA whose expression is modulated by a variety of ligand-receptor interactions and is often coregulated with c-fos (1). This study reports the isolation of a mouse Egr-1 genomic clone, its intron-exon structure, and 935 bp of 5' flanking sequence. The gene spans about 3.8 kb and...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/16.18.8835

    authors: Tsai-Morris CH,Cao XM,Sukhatme VP

    更新日期:1988-09-26 00:00:00

  • Laminin-database v.2.0: an update on laminins in health and neuromuscular disorders.

    abstract::The laminin (LM)-database, hosted at http://www.lm.lncc.br, was published in the NAR database 2011 edition. It was the first database that provided comprehensive information concerning a non-collagenous family of extracellular matrix proteins, the LMs. In its first version, this database contained a large amount of in...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt901

    authors: Golbert DC,Santana-van-Vliet E,Mundstein AS,Calfo V,Savino W,de Vasconcelos AT

    更新日期:2014-01-01 00:00:00

  • Archaeal DnaG contains a conserved N-terminal RNA-binding domain and enables tailing of rRNA by the exosome.

    abstract::The archaeal exosome is a phosphorolytic 3'-5' exoribonuclease complex. In a reverse reaction it synthesizes A-rich RNA tails. Its RNA-binding cap comprises the eukaryotic orthologs Rrp4 and Csl4, and an archaea-specific subunit annotated as DnaG. In Sulfolobus solfataricus DnaG and Rrp4 but not Csl4 show preference f...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku969

    authors: Hou L,Klug G,Evguenieva-Hackenberg E

    更新日期:2014-11-10 00:00:00

  • Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae.

    abstract::Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa545

    authors: Prada-Luengo I,Møller HD,Henriksen RA,Gao Q,Larsen CE,Alizadeh S,Maretty L,Houseley J,Regenberg B

    更新日期:2020-08-20 00:00:00

  • The Saccharomyces cerevisiae RAD9 cell cycle checkpoint gene is required for optimal repair of UV-induced pyrimidine dimers in both G(1) and G(2)/M phases of the cell cycle.

    abstract::Cells respond to DNA damage by activating both cellular growth arrest and DNA repair processes. In Saccharomyces cerevesiae the RAD9 gene controls DNA damage-mediated cell cycle arrest that is known to allow efficient repair. To ascertain whether RAD9 plays a role in DNA repair per se, the removal of UV-induced photol...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/29.10.2020

    authors: Al-Moghrabi NM,Al-Sharif IS,Aboussekhra A

    更新日期:2001-05-15 00:00:00

  • R.E.D. Server: a web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments.

    abstract::R.E.D. Server is a unique, open web service, designed to derive non-polarizable RESP and ESP charges and to build force field libraries for new molecules/molecular fragments. It provides to computational biologists the means to derive rigorously molecular electrostatic potential-based charges embedded in force field l...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr288

    authors: Vanquelef E,Simon S,Marquant G,Garcia E,Klimerak G,Delepine JC,Cieplak P,Dupradeau FY

    更新日期:2011-07-01 00:00:00

  • Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene.

    abstract::Members of the HMG-I(Y) family of mammalian nonhistone proteins are of importance because they have been demonstrated to bind specifically to the minor groove of A.T-rich sequences both in vitro and in vivo and to function as gene transcriptional regulatory proteins in vivo. Here we report the cloning, sequencing, cha...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/21.18.4259

    authors: Friedmann M,Holth LT,Zoghbi HY,Reeves R

    更新日期:1993-09-11 00:00:00

  • Local conformational variations observed in B-DNA crystals do not improve base stacking: computational analysis of base stacking in a d(CATGGGCCCATG)(2) BA intermediate crystal structure.

    abstract::The crystal structure of d(CATGGGCCCATG)(2) shows unique stacking patterns of a stable B<-->A-DNA intermediate. We evaluated intrinsic base stacking energies in this crystal structure using an ab initio quantum mechanical method. We found that all crystal base pair steps have stacking energies close to their values in...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.24.4893

    authors: Poner J,Florián J,Ng HL,Poner JE,Packová N

    更新日期:2000-12-15 00:00:00

  • Updates of the HbVar database of human hemoglobin variants and thalassemia mutations.

    abstract::HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Database records incl...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt911

    authors: Giardine B,Borg J,Viennas E,Pavlidis C,Moradkhani K,Joly P,Bartsakoulia M,Riemer C,Miller W,Tzimas G,Wajcman H,Hardison RC,Patrinos GP

    更新日期:2014-01-01 00:00:00

  • Analysis of erythroid nuclear proteins binding to the promoter and enhancer elements of the chicken histone H5 gene.

    abstract::The chicken erythroid proteins binding to the histone H5 5' promoter and 3' erythroid-specific enhancer regions were identified. In DNase I footprinting and gel mobility shift experiments with immature adult erythrocyte nuclear extracts, we have demonstrated the binding of proteins to the GC-box, a high affinity Sp1 b...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.23.6385

    authors: Sun JM,Penner CG,Davie JR

    更新日期:1992-12-11 00:00:00

  • Type III restriction endonuclease EcoP15I is a heterotrimeric complex containing one Res subunit with several DNA-binding regions and ATPase activity.

    abstract::For efficient DNA cleavage, the Type III restriction endonuclease EcoP15I communicates with two inversely oriented recognition sites in an ATP-dependent process. EcoP15I consists of methylation (Mod) and restriction (Res) subunits forming a multifunctional enzyme complex able to methylate or to cleave DNA. In this stu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr1239

    authors: Wyszomirski KH,Curth U,Alves J,Mackeldanz P,Möncke-Buchner E,Schutkowski M,Krüger DH,Reuter M

    更新日期:2012-04-01 00:00:00

  • AptaBlocks: Designing RNA complexes and accelerating RNA-based drug delivery systems.

    abstract::RNA-based therapeutics, i.e. the utilization of synthetic RNA molecules to alter cellular functions, have the potential to address targets which are currently out of scope for traditional drug design pipelines. This potential however hinges on the ability to selectively deliver and internalize therapeutic RNAs into ce...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gky577

    authors: Wang Y,Hoinka J,Liang Y,Adamus T,Swiderski P,Przytycka TM

    更新日期:2018-09-19 00:00:00

  • Nucleotide sequence from the coding region of rabbit beta-globin messenger RNA.

    abstract::A sequence of 89 nucleotides from rabbit beta-globin mRNA has been determined and is shown to code for residues 107 to 137 of the beta-globin protein. In addition, a sequence heterogeneity has been identified within this 89 nucleotide long sequence which corresponds to a known polymorphic variant of rabbit beta-globin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/3.7.1811

    authors: Proudfoot NJ

    更新日期:1976-07-01 00:00:00

  • Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes.

    abstract::Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed the question whether the methyltransferase and transcriptional co-activ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv776

    authors: Yoo KH,Oh S,Kang K,Hensel T,Robinson GW,Hennighausen L

    更新日期:2015-10-15 00:00:00