Removal of shelterin reveals the telomere end-protection problem.

The telomere end-protection problem is defined by the aggregate of DNA damage signaling and repair pathways that require repression at telomeres. To define the end-protection problem, we removed the whole shelterin complex from mouse telomeres through conditional deletion of TRF1 and TRF2 in nonhomologous end-joining (NHEJ) deficient cells. The data ...
reveal two DNA damage response pathways not previously observed upon deletion of individual shelterin proteins. The shelterin-free telomeres are processed by microhomology-mediated alternative-NHEJ when Ku70/80 is absent and are attacked by nucleolytic degradation in the absence of 53BP1. The data establish that the end-protection problem is specified by six pathways [ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3 related) signaling, classical-NHEJ, alt-NHEJ, homologous recombination, and resection] and show how shelterin acts with general DNA damage response factors to solve this problem.
Mesh Terms:
Animals, Antigens, Nuclear, Cell Cycle, Cell Cycle Proteins, Cells, Cultured, Chromosomal Proteins, Non-Histone, DNA Breaks, Double-Stranded, DNA End-Joining Repair, DNA Ligases, DNA Repair, DNA-Binding Proteins, Homologous Recombination, Mice, Mice, Knockout, Poly(ADP-ribose) Polymerases, Protein-Serine-Threonine Kinases, Signal Transduction, Telomere, Telomere Homeostasis, Telomere-Binding Proteins, Telomeric Repeat Binding Protein 1, Telomeric Repeat Binding Protein 2, Tumor Suppressor Proteins
Science
Date: May. 04, 2012
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