Science · 2009 · 834 citations · 61 references
Life SciencesGeneticsMolecular BiologyChromatin StructureDna RepairGenome OrganizationDna DamageDna Damage SignalingDna Double-strand Break RepairDna Strand BreaksDouble-strand Break RepairTelomere BiologyChromosome End ProtectionDna Damage Repair PathwaysDna Damage Response PathwaysDna Repair At TelomeresProtein ComplexesTelomere End ProtectionTelomere FunctionTelomere Structure
Eukaryotic chromosome ends risk being mistaken for DNA damage, which would trigger cell cycle arrest and genome instability, so they are protected by telomeres. Recent studies show that telomeres disguise chromosome ends by mechanisms adapted to species‑specific DNA damage responses, accounting for their diverse structures.
The ends of eukaryotic chromosomes have the potential to be mistaken for damaged or broken DNA and must therefore be protected from cellular DNA damage response pathways. Otherwise, cells might permanently arrest in the cell cycle, and attempts to “repair” the chromosome ends would have devastating consequences for genome integrity. This end-protection problem is solved by protein-DNA complexes called telomeres. Studies of mammalian cells have recently uncovered the mechanism by which telomeres disguise the chromosome ends. Comparison to unicellular eukaryotes reveals key differences in the DNA damage response systems that inadvertently threaten chromosome ends. Telomeres appear to be tailored to these variations, explaining their variable structure and composition.
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Extension of Life-Span by Introduction of Telomerase into Normal Human Cells
Andrea Bodnár, Michel Ouellette, Maria Frolkis et al. · Science · 1998 · 5K citations
A DNA damage checkpoint response in telomere-initiated senescence
Fabrizio d’Adda di Fagagna, Philip M. Reaper, Lorena Clay-Farrace et al. · Nature · 2003 · 2.8K citations
Mammalian Telomeres End in a Large Duplex Loop
Jack D. Griffith, Laurey Comeau, Soraya I. Rosenfield et al. · Cell · 1999 · 2.4K citations · Full text