Altered Nuclear Functions in Progeroid Syndromes: a Paradigm for Aging Research

Syndromes of accelerated aging could provide an entry point for identifying and dissecting the cellular pathways that are involved in the development of age-related pathologies in the general population. However, their usefulness for aging research has been controversial, as it has been argued that these diseases do not faithfully reflect the process of natural aging. Here we review recent findings on the molecular basis of two progeroid diseases, Werner syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS), and highlight functional connections to cellular processes that may contribute to normal aging.

• Publication year

  2009

• Venue

  TheScientificWorldJournal

• Publication date

  2009-12-16

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1100/tsw.2009.159PMID 20024518PMCID 4213125
• 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.

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  2009cited by this paper
• Telomere length in Hutchinson-Gilford progeria syndrome.

  2009cited by this paper
• Sequence-specific processing of telomeric 3' overhangs by the Werner syndrome protein exonuclease activity

  2009cited by this paper
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  2009cited by this paper
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  2008cited by this paper
• Perturbation of wild‐type lamin A metabolism results in a progeroid phenotype

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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2007cited by this paper
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  2007cited by this paper
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  2007influential reference
• Deletion of Ku70, Ku80, or Both Causes Early Aging without Substantially Increased Cancer

  2007cited by this paper
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  2007cited by this paper
• The Mutant Form of Lamin A that Causes Hutchinson-Gilford Progeria Is a Biomarker of Cellular Aging in Human Skin

  2007cited by this paper
• Hutchinson–Gilford progeria syndrome: Review of the phenotype

  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
• Dynamic roles for G4 DNA in the biology of eukaryotic cells

  2006cited by this paper
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  2006cited by this paper
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  2006cited by this paper
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  2005cited by this paper
• Shelterin: the protein complex that shapes and safeguards human telomeres.

  2005cited by this paper
• The Pso4 mRNA Splicing and DNA Repair Complex Interacts with WRN for Processing of DNA Interstrand Cross-links*

  2005cited by this paper
• Rescue of heterochromatin organization in Hutchinson-Gilford progeria by drug treatment

  2005cited by this paper
• POT1 Stimulates RecQ Helicases WRN and BLM to Unwind Telomeric DNA Substrates*

  2005cited by this paper
• Genome instability in progeria: when repair gets old

  2005cited by this paper
• Human Ku70/80 interacts directly with hTR, the RNA component of human telomerase

  2005cited by this paper
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  2005cited by this paper
• Blocking protein farnesyltransferase improves nuclear blebbing in mouse fibroblasts with a targeted Hutchinson-Gilford progeria syndrome mutation.

  2005cited by this paper
• Blocking protein farnesyltransferase improves nuclear shape in fibroblasts from humans with progeroid syndromes.

  2005cited by this paper
• Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway.

  2005cited by this paper
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  2005cited by this paper
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  2005cited by this paper
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  2005cited by this paper
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  2005cited by this paper
• Proteins that bind A-type lamins: integrating isolated clues

  2004cited by this paper
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  2004influential reference
• Laminopathies

  2004cited by this paper
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  2004cited by this paper
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  2004cited by this paper
• Essential role of limiting telomeres in the pathogenesis of Werner syndrome

  2004cited by this paper
• Poly(ADP-ribose) polymerase 1 regulates both the exonuclease and helicase activities of the Werner syndrome protein.

  2004cited by this paper
• TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of telomeric DNA

  2004influential reference
• Cell cycle-dependent regulation of yeast telomerase by Ku

  2004cited by this paper
• Genome‐scale expression profiling of Hutchinson–Gilford progeria syndrome reveals widespread transcriptional misregulation leading to mesodermal/mesenchymal defects and accelerated atherosclerosis

  2004cited by this paper
• Indecent exposure: when telomeres become uncapped.

  2004cited by this paper
• Defective Telomere Lagging Strand Synthesis in Cells Lacking WRN Helicase Activity

  2004cited by this paper
• Hutchinson–Gilford progeria syndrome

  2004cited by this paper
• Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson–Gilford progeria syndrome

  2004cited by this paper
• Homologous recombination generates T-loop-sized deletions at human telomeres.

  2004cited by this paper
• Telomere Shortening Exposes Functions for the Mouse Werner and Bloom Syndrome Genes

  2004cited by this paper
• A means to a DNA end: the many roles of Ku

  2004cited by this paper
• Functional links between telomeres and proteins of the DNA-damage response.

  2004cited by this paper
• Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends.

  2003cited by this paper
• Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome

  2003cited by this paper
• A progeroid syndrome in mice is caused by defects in A-type lamins

  2003cited by this paper
• Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia.

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

  2003cited by this paper
• The laminopathies: nuclear structure meets disease.

  2003cited by this paper
• Lamin A Truncation in Hutchinson-Gilford Progeria

  2003cited by this paper
• Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus.

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

  2002cited by this paper
• Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70

  2002cited by this paper
• Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase–deficient mice

  2002cited by this paper
• Senescence Induced by Altered Telomere State, Not Telomere Loss

  2002cited by this paper
• HUTCHINSON-GILFORD PROGERIA SYNDROME: A PATHOLOGIC STUDY

  2002cited by this paper
• Werner Protein Is a Target of DNA-dependent Protein Kinase in Vivo and in Vitro, and Its Catalytic Activities Are Regulated by Phosphorylation*

  2002cited by this paper
• Colocalization, Physical, and Functional Interaction between Werner and Bloom Syndrome Proteins*

  2002cited by this paper
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  2002cited by this paper
• Displacement of DNA-PKcs from DNA ends by the Werner syndrome protein.

  2002cited by this paper
• Telomere-binding Protein TRF2 Binds to and Stimulates the Werner and Bloom Syndrome Helicases*

  2002cited by this paper
• Nuclear lamins: building blocks of nuclear architecture.

  2002cited by this paper
• The Bloom's and Werner's syndrome proteins are DNA structure-specific helicases

  2001cited by this paper
• Inner nuclear membrane proteins: functions and targeting

  2001cited by this paper
• A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA.

  2001cited by this paper
• Gene profile of replicative senescence is different from progeria or elderly donor.

  2001cited by this paper
• Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity

  2001cited by this paper
• Requirements for the Nucleolytic Processing of DNA Ends by the Werner Syndrome Protein-Ku70/80 Complex*

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

  2000cited by this paper
• Nuclear organization of DNA replication in primary mammalian cells.

  2000cited by this paper
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  2000influential reference
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  2000cited by this paper
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  2000cited by this paper
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  2000cited by this paper
• Nuclear Lamins a and B1

  2000cited by this paper
• The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations.

  2000cited by this paper
• DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation

  2000cited by this paper
• Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA.

  2000cited by this paper
• Functional interaction between the Werner Syndrome protein and DNA polymerase delta.

  2000cited by this paper

• Recent advances in understanding the role of lamins in health and disease

  2016cites this paper
• Stem cell aging in adult progeria

  2015cites this paper
• A filtering strategy identifies FOXQ1 as a potential effector of lamin A dysfunction

  2012cites this paper
• Oxidative stress induces an ATM‐independent senescence pathway through p38 MAPK‐mediated lamin B1 accumulation

  2012cites this paper
• Hutchinson-Gilford progeria syndrome, cardiovascular disease and oxidative stress.

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  2011cites this paper
• Lack of association of the WRN C1367T polymorphism with senile cataract in the Israeli population

  2010cites this paper