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Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal.

Shelterin is an essential telomeric protein complex that prevents DNA damage signaling and DNA repair at mammalian chromosome ends. Here we report on the role of the TRF2-interacting factor Rap1, a conserved shelterin subunit of unknown function. We removed Rap1 from mouse telomeres either through gene deletion or by replacing TRF2 with a mutant that does not bind Rap1. Rap1 was dispensable for the essential functions of TRF2--repression of ATM kinase signaling and nonhomologous end joining (NHEJ)--and mice lacking telomeric Rap1 were viable and fertile. However, Rap1 was critical for the repression of homology-directed repair (HDR), which can alter telomere length. The data reveal that HDR at telomeres can take place in the absence of DNA damage foci and underscore the functional compartmentalization within shelterin.

Pubmed ID: 20339076

Authors

  • Sfeir A
  • Kabir S
  • van Overbeek M
  • Celli GB
  • de Lange T

Journal

Science (New York, N.Y.)

Publication Data

March 26, 2010

Associated Grants

  • Agency: NIA NIH HHS, Id: AG016642
  • Agency: NIGMS NIH HHS, Id: GM049046
  • Agency: NIA NIH HHS, Id: R01 AG016642
  • Agency: NIA NIH HHS, Id: R01 AG016642-01
  • Agency: NIA NIH HHS, Id: R01 AG016642-02
  • Agency: NIA NIH HHS, Id: R01 AG016642-03
  • Agency: NIA NIH HHS, Id: R01 AG016642-04
  • Agency: NIA NIH HHS, Id: R01 AG016642-05
  • Agency: NIA NIH HHS, Id: R01 AG016642-06
  • Agency: NIA NIH HHS, Id: R01 AG016642-07
  • Agency: NIA NIH HHS, Id: R01 AG016642-08
  • Agency: NIA NIH HHS, Id: R01 AG016642-09
  • Agency: NIA NIH HHS, Id: R01 AG016642-10
  • Agency: NIA NIH HHS, Id: R01 AG016642-11
  • Agency: NIGMS NIH HHS, Id: R01 GM049046
  • Agency: NIGMS NIH HHS, Id: R01 GM049046-07
  • Agency: NIGMS NIH HHS, Id: R01 GM049046-08
  • Agency: NIGMS NIH HHS, Id: R01 GM049046-09
  • Agency: NIGMS NIH HHS, Id: R01 GM049046-10
  • Agency: NIGMS NIH HHS, Id: R01 GM049046-11
  • Agency: NIGMS NIH HHS, Id: R01 GM049046-12
  • Agency: NIGMS NIH HHS, Id: R37 GM049046
  • Agency: NIGMS NIH HHS, Id: R37 GM049046-13
  • Agency: NIGMS NIH HHS, Id: R37 GM049046-14
  • Agency: NIGMS NIH HHS, Id: R37 GM049046-15
  • Agency: NIGMS NIH HHS, Id: R37 GM049046-16
  • Agency: NIGMS NIH HHS, Id: R37 GM049046-17

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Proliferation
  • Cells, Cultured
  • Checkpoint Kinase 2
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins
  • Gene Deletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Sequence Data
  • Protein-Serine-Threonine Kinases
  • Recombination, Genetic
  • Signal Transduction
  • Sister Chromatid Exchange
  • Telomere
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 2
  • Tumor Suppressor Proteins