How shelterin protects mammalian telomeres.
The genomes of prokaryotes and eukaryotic organelles are usually circular as are most plasmids and viral genomes. In contrast, the nuclear genomes of eukaryotes are organized on linear chromosomes, which require mechanisms to protect and replicate DNA ends. Eukaryotes navigate these problems with the advent of telomeres, protective nucleoprotein complexes at the ends of linear chromosomes, and telomerase, the enzyme that maintains the DNA in these structures. Mammalian telomeres contain a specific protein complex, shelterin, that functions to protect chromosome ends from all aspects of the DNA damage response and regulates telomere maintenance by telomerase. Recent experiments, discussed here, have revealed how shelterin represses the ATM and ATR kinase signaling pathways and hides chromosome ends from nonhomologous end joining and homology-directed repair.
Palm
Wilhelm
W
Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10021, USA.
de Lange
Titia
T
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D005057:Eukaryotic Cells; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000089804:Shelterin Complex; D015398:Signal Transduction; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D046912:Multiprotein Complexes; D012097:Repressor Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D004247:DNA