Type your tag names separated by a space and hit enter
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.
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins
Chromosomal Proteins, Non-Histone
DNA Breaks, Double-Stranded
DNA End-Joining Repair
Telomeric Repeat Binding Protein 1
Telomeric Repeat Binding Protein 2
Tumor Suppressor Proteins
Pub Type(s)Journal Article
Research Support, N.I.H., Extramural