Recent expansion of the telomeric complex in rodents: Two distinct POT1 proteins protect mouse telomeres.
Human telomeres are protected by shelterin, a complex that includes the POT1 single-stranded DNA binding protein. We found that mouse telomeres contain two POT1 paralogs, POT1a and POT1b, and we used conditional deletion to determine their function. Double-knockout cells showed that POT1a/b are required to prevent a DNA damage signal at chromosome ends, endoreduplication, and senescence. In contrast, POT1a/b were largely dispensable for repression of telomere fusions. Single knockouts and complementation experiments revealed that POT1a and POT1b have distinct functions. POT1a, but not POT1b, was required to repress a DNA damage signal at telomeres. Conversely, POT1b, but not POT1a, had the ability to regulate the amount of single-stranded DNA at the telomere terminus. We conclude that mouse telomeres require two distinct POT1 proteins whereas human telomeres have one. Such divergence is unprecedented in mammalian chromosome biology and has implications for modeling human telomere biology in mice.
Hockemeyer
Dirk
D
Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Daniels
Jan-Peter
JP
Takai
Hiroyuki
H
de Lange
Titia
T
D000818:Animals; D002455:Cell Division / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004277:DNA, Single-Stranded / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D005804:Genes, Lethal / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000235:genetics; D013045:Species Specificity; D016615:Telomere / Q000235:genetics*; D034501:Telomere-Binding Proteins / Q000235:genetics; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C507326:POT1 protein, mouse; C512707:POT1b protein, mouse; D020033:Protein Isoforms; D012097:Repressor Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D035341:Telomeric Repeat Binding Protein 2