Fanconi anemia protein FANCD2 inhibits TRF1 polyADP-ribosylation through tankyrase1-dependent manner

BackgroundFanconi anemia (FA) is a rare autosomal recessive syndrome characterized by developmental abnormalities, progressive bone marrow failure, and predisposition to cancer. The key FA protein FANCD2 crosstalks with members of DNA damage and repair pathways that also play a role at telomeres. Therefore, we investigated whether FANCD2 has a similar involvement at telomeres.ResultsWe reveal that FANCD2 may perform a novel function separate to the FANCD2/BRCA pathway. This function includes FANCD2 interaction with one of the telomere components, the PARP family member tankyrase-1. Moreover, FANCD2 inhibits tankyrase-1 activity in vitro. In turn, FANCD2 deficiency increases the polyADP-ribosylation of telomere binding factor TRF1.ConclusionsFANCD2 binding and inhibiting tankyrase-1PARsylation at telomeres may provide an additional step within the FA pathway for the regulation of genomic integrity.

• Publication year

  2011

• Venue

  Genome Integrity

• Publication date

  2011-02-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/2041-9414-2-4PMID 21314979PMCID 3048478
• 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.

• Radiation-induced DNA damage and repair in human γδ and αβ T-lymphocytes analysed by the alkaline comet assay

  2010influential reference
• Constitutive Activation of Caspase-3 and Poly ADP Ribose Polymerase Cleavage in Fanconi Anemia Cells

  2010cited by this paper
• How Telomeres Solve the End-Protection Problem

  2009cited by this paper
• DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity

  2009influential reference
• How Telomeres Solve the End-Protection Problem

  2009cited by this paper
• A role for monoubiquitinated FANCD2 at telomeres in ALT cells

  2009cited by this paper
• Fanconi anemia proteins and endogenous stresses.

  2009cited by this paper
• Control of telomere length by a trimming mechanism that involves generation of t-circles

  2009cited by this paper
• How the fanconi anemia pathway guards the genome.

  2009cited by this paper
• HPV-16 E7 reveals a link between DNA replication stress, fanconi anemia D2 protein, and alternative lengthening of telomere-associated promyelocytic leukemia bodies.

  2008cited by this paper
• Telomere elongation by a mutant tankyrase 1 without TRF1 poly(ADP-ribosyl)ation.

  2008cited by this paper
• Replication and protection of telomeres

  2007cited by this paper
• TPP1 is a homologue of ciliate TEBP-β and interacts with POT1 to recruit telomerase

  2007cited by this paper
• A topological mechanism for TRF2-enhanced strand invasion

  2007cited by this paper
• Fanconi anemia and DNA replication repair.

  2007cited by this paper
• The epigenetic regulation of mammalian telomeres

  2007cited by this paper
• Histone H2AX and Fanconi anemia FANCD2 function in the same pathway to maintain chromosome stability

  2007cited by this paper
• Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins

  2007cited by this paper
• Dedicated to the core: understanding the Fanconi anemia complex.

  2006cited by this paper
• Fanconi anaemia genes and susceptibility to cancer

  2006cited by this paper
• Flow cytometry and FISH to measure the average length of telomeres (flow FISH)

  2006cited by this paper
• Molecular pathogenesis of Fanconi anemia: recent progress.

  2006cited by this paper
• Fanconi's anaemia and related bone marrow failure syndromes.

  2006cited by this paper
• Regulation of DNA repair by ubiquitylation

  2006cited by this paper
• Telomere-related genome instability in cancer.

  2005influential reference
• Direct DNA Binding Activity of the Fanconi Anemia D2 Protein*

  2005cited by this paper
• The first molecular details of ALT in human tumor cells.

  2005influential reference
• Accelerated Telomere Shortening and Telomere Abnormalities in Radiosensitive Cell Lines

  2005cited by this paper
• Homologous recombination generates T-loop-sized deletions at human telomeres.

  2004cited by this paper
• Molecular cross-talk among chromosome fragility syndromes.

  2004cited by this paper
• Telomere dysfunction in genome instability syndromes.

  2004cited by this paper
• POT1 as a terminal transducer of TRF1 telomere length control

  2003influential reference
• TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres.

  2003cited by this paper
• Abnormal telomere metabolism in Fanconi's anaemia correlates with genomic instability and the probability of developing severe aplastic anaemia

  2003cited by this paper
• Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia.

  2002cited by this paper
• Role for the Related Poly(ADP-Ribose) Polymerases Tankyrase 1 and 2 at Human Telomeres

  2002cited by this paper
• Telomere length measurement by Q-FISH.

  2001influential reference
• Telomere shortening in Fanconi anaemia demonstrated by a direct FISH approach

  2001cited by this paper
• Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway.

  2001cited by this paper
• Tankyrase promotes telomere elongation in human cells.

  2000cited by this paper
• Mammalian telomeres end in a large duplex loop.

  1999cited by this paper
• TIN2, a new regulator of telomere length in human cells

  1999cited by this paper
• Accelerated telomere shortening and telomerase activation in Fanconi's anaemia

  1999cited by this paper
• Telomeres do D-loop-T-loop.

  1999cited by this paper
• Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.

  1998influential reference
• Footprint analysis of estrogen receptor binding to adjacent estrogen response elements.

  1996cited by this paper
• Identification of potential active-site residues in the human poly(ADP-ribose) polymerase.

  1993cited by this paper
• A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.

  1988cited by this paper
• The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity.

  1987cited by this paper
• A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon.

  1973cited by this paper
• Origin of concatemeric T7 DNA.

  1972cited by this paper
• Origin of Concatemeric T7DNA

  1972cited by this paper
• Sugar and Disease

  1972cited by this paper

• PARP (Poly ADP‐ribose Polymerase) Family in Health and Disease

  2025cites this paper
• Insights of tankyrases: A novel target for drug discovery.

  2020cites this paper
• Genetic Syndromes and Aging

  2019cites this paper
• Models, Molecules and Mechanisms in Biogerontology: Physiological Abnormalities, Diseases and Interventions

  2019cites this paper
• Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

  2017cites this paper
• TERT promoter mutations in telomere biology.

  2017cites this paper
• Tankyrase inhibition aggravates kidney injury in the absence of CD2AP

  2016cites this paper
• Fanconi anemia proteins in telomere maintenance.

  2016cites this paper
• Impact des dérégulations de p53 : du syndrome Li-Fraumeni aux syndromes d'insuffisance médullaire héréditaire

  2016cites this paper
• PARP and Carcinogenesis

  2015cites this paper
• TIPs: Tankyrase Interacting Proteins

  2015cites this paper
• Structure and Functions of Telomeres in Organismal Homeostasis and Disease

  2015cites this paper
• Genomic Elements in Health, Disease and Evolution

  2015cites this paper
• Visualization and quantitative analysis of extrachromosomal telomere-repeat DNA in individual human cells by Halo-FISH

  2015cites this paper
• Tankyrases: Structure, Function and Therapeutic Implications in Cancer

  2014cites this paper
• TRF1 and TRF2 Differentially Modulate Rad51-Mediated Telomeric and Nontelomeric Displacement Loop Formation in Vitro

  2014cites this paper
• Telomere dysfunction and hematologic disorders.

  2014cites this paper
• Telomeropathies: An emerging spectrum disorder

  2014cites this paper
• Cell biology of disease Telomeropathies : An emerging spectrum disorder

  2014cites this paper
• Genética Clínica de la anemia de Fanconi

  2013cites this paper
• Identification of novel factors controlling DNA damage responses at uncapped telomeres

  2013cites this paper
• Tankyrases as drug targets

  2013cites this paper
• Posttranslational control of telomere maintenance and the telomere damage response

  2012cites this paper
• Dysfunctional telomeres in primary cells from Fanconi anemia FANCD2 patients

  2012cites this paper
• TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase)

  2012cites this paper
• Direct Inhibition of TNF-α Promoter Activity by Fanconi Anemia Protein FANCD2

  2011cites this paper