Genome maintenance and transcription integrity in aging and disease

DNA damage contributes to cancer development and aging. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated aging (Schumacher et al., 2008). DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007). Cellular response mechanisms to stalled RNA polymerase II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the aging organism (Garinis et al., 2009). Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in aging and disease. We discuss how the nucleotide excision repair system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer.

• Publication year

  2013

• Venue

  Frontiers in Genetics

• Publication date

  2013-02-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fgene.2013.00019PMID 23443494PMCID 3580961
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Genome maintenance and transcription integrity in aging and disease

  2013cited by this paper
• XPG and XPF endonucleases trigger chromatin looping and DNA demethylation for accurate expression of activated genes.

  2012cited by this paper
• Nucleotide excision repair: new tricks with old bricks.

  2012cited by this paper
• The telomere syndromes

  2012cited by this paper
• Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in transcription-coupled DNA repair

  2012cited by this paper
• The p53 network: cellular and systemic DNA damage responses in aging and cancer.

  2012cited by this paper
• SHINING A LIGHT ON XERODERMA PIGMENTOSUM

  2012cited by this paper
• UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair

  2012cited by this paper
• DNA damage, chromatin, and transcription: the trinity of aging.

  2012cited by this paper
• Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair

  2012cited by this paper
• Defective transcription initiation causes postnatal growth failure in a mouse model of nucleotide excision repair (NER) progeria

  2012cited by this paper
• Playing the end game: DNA double-strand break repair pathway choice.

  2012cited by this paper
• DNA repair endonuclease ERCC1–XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy

  2012cited by this paper
• A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells.

  2011cited by this paper
• Cdc48/p97 mediates UV-dependent turnover of RNA Pol II.

  2011cited by this paper
• DNA repair deficiency in neurodegeneration.

  2011cited by this paper
• DNA interstrand crosslink repair and cancer

  2011cited by this paper
• A history of TFIIH: two decades of molecular biology on a pivotal transcription/repair factor.

  2011cited by this paper
• Real-Time Observation of Transcription Initiation and Elongation on an Endogenous Yeast Gene

  2011cited by this paper
• The DNA damage response: making it safe to play with knives.

  2010cited by this paper
• Human SIRT6 Promotes DNA End Resection Through CtIP Deacetylation

  2010cited by this paper
• Insulin-like growth factor 1 treatment extends longevity in a mouse model of human premature aging by restoring somatotroph axis function

  2010cited by this paper
• Stochastic and reversible assembly of a multiprotein DNA repair complex ensures accurate target site recognition and efficient repair

  2010cited by this paper
• Expanded roles of the Fanconi anemia pathway in preserving genomic stability.

  2010influential reference
• The Fanconi anemia pathway and ICL repair: implications for cancer therapy

  2010cited by this paper
• A two-step model for senescence triggered by a single critically short telomere

  2010cited by this paper
• Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome

  2010cited by this paper
• NER factors are recruited to active promoters and facilitate chromatin modification for transcription in the absence of exogenous genotoxic attack.

  2010influential reference
• Transcription and replication

  2010cited by this paper
• Defective DSB repair correlates with abnormal nuclear morphology and is improved with FTI treatment in Hutchinson-Gilford progeria syndrome fibroblasts.

  2010cited by this paper
• Neuronal IGF‐1 resistance reduces Aβ accumulation and protects against premature death in a model of Alzheimer's disease

  2009cited by this paper
• The DNA-damage response in human biology and disease

  2009cited by this paper
• A two-step model for senescence triggered by a single critically short telomere

  2009cited by this paper
• Reduced IGF-1 signaling delays age-associated proteotoxicity in mice.

  2009cited by this paper
• Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity

  2009cited by this paper
• Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevity

  2009cited by this paper
• Transcription‐blocking DNA damage in aging: a mechanism for hormesis

  2009cited by this paper
• How Telomeres Solve the End-Protection Problem

  2009cited by this paper
• Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

  2009cited by this paper
• The somatotropic axis and aging: mechanisms and persistent questions about practical implications.

  2009cited by this paper
• The role of the DNA damage response in neuronal development, organization and maintenance.

  2008cited by this paper
• Age to survive: DNA damage and aging.

  2008influential reference
• Advances in chemical carcinogenesis: a historical review and prospective.

  2008cited by this paper
• Werner protein cooperates with the XRCC4-DNA ligase IV complex in end-processing.

  2008cited by this paper
• Rising from the RecQ-age: the role of human RecQ helicases in genome maintenance.

  2008cited by this paper
• Transcription-coupled DNA repair: two decades of progress and surprises

  2008cited by this paper
• Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer

  2008cited by this paper
• DNA damage checkpoints: from initiation to recovery or adaptation.

  2007cited by this paper
• The DNA damage response: ten years after.

  2007cited by this paper
• The resurgence of platinum-based cancer chemotherapy

  2007cited by this paper
• Tissue specific mutagenic and carcinogenic responses in NER defective mouse models.

  2007cited by this paper
• Physical and functional interactions between Werner syndrome helicase and mismatch-repair initiation factors

  2007cited by this paper
• Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1.

  2007cited by this paper
• Collaboration of Werner syndrome protein and BRCA1 in cellular responses to DNA interstrand cross-links

  2006influential reference
• Human progeroid syndromes, aging and cancer: new genetic and epigenetic insights into old questions

  2006cited by this paper
• Impaired Genome Maintenance Suppresses the Growth Hormone–Insulin-Like Growth Factor 1 Axis in Mice with Cockayne Syndrome

  2006cited by this paper
• Werner syndrome protein participates in a complex with RAD51, RAD54, RAD54B and ATR in response to ICL-induced replication arrest

  2006influential reference
• Cockayne syndrome B protein regulates the transcriptional program after UV irradiation

  2006cited by this paper
• Pharmacokinetics, Metabolism, and Routes of Excretion of Intravenous Irofulven in Patients with Advanced Solid Tumors

  2006cited by this paper
• Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.

  2006cited by this paper
• A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis

  2006cited by this paper
• Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation

  2005cited by this paper
• Dyskeratosis congenita: telomerase, telomeres and anticipation.

  2005cited by this paper
• Genomic instability in laminopathy-based premature aging

  2005influential reference
• Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis.

  2004cited by this paper
• Transcription — guarding the genome by sensing DNA damage

  2004influential reference
• Database of mouse strains carrying targeted mutations in genes affecting biological responses to DNA damage Version 7.

  2004cited by this paper
• Linkage between Werner Syndrome Protein and the Mre11 Complex via Nbs1*

  2004cited by this paper
• DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy.

  2003cited by this paper
• Association between telomere length in blood and mortality in people aged 60 years or older.

  2003cited by this paper
• RecQ helicases: caretakers of the genome

  2003cited by this paper
• WRN Interacts Physically and Functionally with the Recombination Mediator Protein RAD52*

  2003cited by this paper
• Central Role for the Werner Syndrome Protein/Poly(ADP-Ribose) Polymerase 1 Complex in the Poly(ADP-Ribosyl)ation Pathway after DNA Damage

  2003cited by this paper
• ATM and related protein kinases: safeguarding genome integrity

  2003cited by this paper
• A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan.

  2002influential reference
• Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways.

  2002cited by this paper
• DNA and its associated processes as targets for cancer therapy

  2002cited by this paper
• S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51.

  2002cited by this paper
• Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription

  2002cited by this paper
• TFIIH plays an essential role in RNA polymerase I transcription.

  2002cited by this paper
• BRCA2 is required for homology-directed repair of chromosomal breaks.

  2001cited by this paper
• A Conserved Regulatory System Minireview for Aging

  2001cited by this paper
• DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency.

  2001cited by this paper
• Genome maintenance mechanisms for preventing cancer

  2001cited by this paper
• An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele

  2001cited by this paper
• Homologous recombination: from model organisms to human disease

  2001cited by this paper
• Macromolecular dynamics in living cell nuclei revealed by fluorescence redistribution after photobleaching

  2001cited by this paper
• Disruption of the Cockayne Syndrome B Gene Impairs Spontaneous Tumorigenesis in Cancer-Predisposed Ink4a/ARF Knockout Mice

  2001cited by this paper
• Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair

  2001cited by this paper
• Ku complex interacts with and stimulates the Werner protein.

  2000cited by this paper
• Cancer predisposition caused by elevated mitotic recombination in Bloom mice

  2000cited by this paper
• Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress.

  2000cited by this paper
• Surfing the p53 network

  2000cited by this paper
• Brca1 controls homology-directed DNA repair.

  1999cited by this paper
• The Werner syndrome protein is involved in RNA polymerase II transcription.

  1999cited by this paper
• Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells.

  1997cited by this paper
• Fludarabine triphosphate inhibits nucleotide excision repair of cisplatin-induced DNA adducts in vitro.

  1997cited by this paper
• The wee1 protein kinase is required for radiation-induced mitotic delay

  1992cited by this paper
• Control of G2 delay by the RAD9 gene of Saccharomyces cerevisiae

  1989cited by this paper
• Rate of depurination of native deoxyribonucleic acid.

  1972cited by this paper

• Roles of base and nucleotide excision repair activities in cancer treatment: implications for prognosis and resistance to therapy in breast and colorectal cancers.

  2026cites this paper
• A multi-omics molecular landscape of 30 tissues in aging female rhesus macaques

  2025cites this paper
• Loss of genome maintenance is linked to mTOR complex 1 signaling and accelerates podocyte damage

  2025cites this paper
• Transport of DNA repair proteins to the cell nucleus by the classical nuclear importin pathway - a structural overview.

  2025cites this paper
• Developmental Heat Conditioning Alters the Adult Glucocorticoid Response and DNA Damage While Mediating Lifespan Variation in Zebra Finches (Taeniopygia Castanotis).

  2025cites this paper
• Transcriptomic entropy reveals tissue-specific patterns in aging and predicts cancer progression

  2025cites this paper
• DNA damage–induced EMT controlled by the PARP-dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells

  2024cites this paper
• DNA damage-induced PARP/ALC1 activation leads to Epithelial-to-Mesenchymal transition stimulating homologous recombination

  2024cites this paper
• Telomere Length, Mitochondrial DNA, and Micronucleus Yield in Response to Oxidative Stress in Peripheral Blood Mononuclear Cells

  2024cites this paper
• High Glucose Increases DNA Damage and Elevates the Expression of Multiple DDR Genes

  2023cites this paper
• Molecular chaperones in DNA repair mechanisms: Role in genomic instability and proteostasis in cancer.

  2022cites this paper
• A high-throughput 384-well CometChip platform reveals a role for 3-methyladenine in the cellular response to etoposide-induced DNA damage

  2022cites this paper
• Analysis of DNA Repair-Related Prognostic Function and Mechanism in Gastric Cancer

  2022cites this paper
• Dynamic Modelling of DNA Repair Pathway at the Molecular Level: A New Perspective

  2022cites this paper
• A score of DNA damage repair pathway with the predictive ability for chemotherapy and immunotherapy is strongly associated with immune signaling pathway in pan-cancer

  2022cites this paper
• A matter of delicate balance: Loss and gain of Cockayne syndrome proteins in premature aging and cancer

  2022cites this paper
• The emerging relationship between metabolism and DNA repair

  2021cites this paper
• Genome Conformity of In Vitro Cultures of Date Palm

  2021cites this paper
• Genome stability in Caenorhabditis elegans

  2021cites this paper
• Potential effect of EGCG on the anti-tumor efficacy of metformin in melanoma cells

  2021cites this paper
• Amplification of RAD54B promotes progression of hepatocellular carcinoma via activating the Wnt/β-catenin signaling

  2021cites this paper
• The Relevance of G-Quadruplexes for DNA Repair

  2021cites this paper
• DNA Damage/Repair Management in Cancers

  2020cites this paper
• Déjà vu All Over Again: A Unitary Biological Mechanism for Intelligence Is (Probably) Untenable

  2020cites this paper
• DNA damage activates mTORC1 signaling in podocytes leading to glomerulosclerosis

  2020cites this paper
• From quality control to neurodegeneration : regulation of autophagy and the DNA damage response by ubiquitin-modifying enzymes

  2020cites this paper
• Hypomethylation of mismatch repair genes MLH1 and MSH2 is associated with chemotolerance of breast carcinoma: Clinical significance

  2018cites this paper
• Visual detection of cyclobutane pyrimidine dimer DNA damage lesions by Hg2+ and carbon dots.

  2018cites this paper
• An epigenetic biomarker of aging for lifespan and healthspan

  2018cites this paper
• Newly Revised Quantitative PCR‐Based Assay for Mitochondrial and Nuclear DNA Damage

  2018cites this paper
• NAMPT nicotinamide phosphoribosyltransferase NMN nicotinamide mononucleotide NMNAT nicotinamide nucleotide adenylyltransferase OLA olaparib PAR poly(ADP-ribose) PARP poly(ADP-ribose) polymerase PARPi PARP inhibitors PIC piceatannol Rsv trans-resveratrol Nicotinamide Adenine Dinucleotide (NAD) and Ce

  2018cites this paper
• The enigmatic oncogene and tumor suppressor‐like properties of RAD54B: Insights into genome instability and cancer

  2017cites this paper
• Arginine CGA codons as a source of nonsense mutations: a possible role in multivariant gene expression, control of mRNA quality, and aging

  2017cites this paper
• Next generation testing strategy for assessment of genomic damage: A conceptual framework and considerations

  2017cites this paper
• UNDERSTANDING THE MECHANISM OF GENOMIC INSTABILITY DURING REPLICATIVE AGING IN BUDDING YEAST

  2017cites this paper
• Identification of rare gene variants in South African breast cancer families through next generation sequencing

  2017cites this paper
• A New Insight into the Development of Novel Anti-Cancer Drugs that Improve the Expression of Mitochondrial Function-Associated Genes

  2017cites this paper
• Mechanisms of DNA damage, repair, and mutagenesis

  2017cites this paper
• DNA Damage Repair System in Plants: A Worldwide Research Update

  2017cites this paper
• Genome instability: Linking ageing and brain degeneration.

  2017cites this paper
• The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery

  2017cites this paper
• A multidimensional omics analysis of the DNA damage response in Caenorhabditis elegans

  2017cites this paper
• Does transcription-associated DNA damage limit lifespan?

  2016cites this paper
• Systemic DNA damage responses in aging and diseases.

  2016cites this paper
• In the Wnt-er of life: Wnt signalling in melanoma and ageing

  2016cites this paper
• New oligonucleotide derivatives as unreactive substrate analogues and potential inhibitors of human apurinic/apyrimidinic endonuclease APE1.

  2016cites this paper
• Genome Stability in Caenorhabditis elegans

  2016cites this paper
• Analysis of the Genetic Requirements for Rad51-Mediated 3’ Polymerization during DNA Repair by Homologous Recombination

  2016cites this paper
• A C. elegans homolog for the UV-hypersensitivity syndrome disease gene UVSSA.

  2016cites this paper
• Alterations in peroxisomal function induced by genomic instability and their relevance for aging

  2016cites this paper
• Detection of DNA damage in peripheral blood mononuclear cells from pancreatic cancer patients

  2015cites this paper
• Quality control mechanisms in cellular and systemic DNA damage responses.

  2015cites this paper
• Role of DNA repair in host immune response and inflammation.

  2015cites this paper
• UNIVERSIDADE FEDERAL DO PARÁ INSTITUTO DE CIÊNCIAS BIOLÓGICAS PROGRAMA DE PÓS-GRADUAÇÃO EM NEUROCIÊNCIAS E BIOLOGIA CELULAR LABORATÓRIO DE FARMACOLOGIA MOLECULAR

  2015cites this paper
• Transcriptional Regulation of the Human Genes that Encode DNA Repair- and Mitochondrial Function-Associated Proteins

  2015cites this paper
• Longevity through DNA damage tolerance

  2015cites this paper
• Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms

  2015cites this paper
• DAF-16/FoxO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage

  2014cites this paper
• Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.

  2014cites this paper
• Genetics of aging, progeria and lamin disorders.

  2014cites this paper
• Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs

  2014cites this paper
• Molecular characterization of the UV-response in Caenorhabditis elegans

  2014cites this paper
• GHK, the Human Skin Remodeling Peptide, Induces Anti-Cancer Expression of Numerous Caspase, Growth Regulatory, and DNA Repair Genes

  2014cites this paper
• Insights into MYC biology through investigation of synthetic lethal interactions with MYC deregulation

  2014cites this paper
• Diet and genome health

  2013cites this paper
• Genetic and environmental influence on DNA strand break repair: A twin study

  2013cites this paper
• Natural compounds with anti-ageing activity.

  2013cites this paper
• Phytoagents for Cancer Management: Regulation of Nucleic Acid Oxidation, ROS, and Related Mechanisms

  2013cites this paper
• Nucleic Acid Oxidation in Human Health and Disease

  2013cites this paper