PHOSPHORYLATION OF THE OXYTRICHA TELOMERE PROTEIN - POSSIBLE CELL-CYCLE REGULATION

In the macronucleus of the ciliate Oxytricha nova, telomeres end with single-stranded (T(4)G(4))(2) DNA bound to a heterodimeric telomere pr otein (alpha beta) Both the alpha and beta subunits (alpha-TP and beta -TP) were phosphorylated in asynchronously growing Oxytricha; beta-TP was phosphorylated to a much higher degree, In vitro, mouse cyclin-dep endent kinases (Cdks) phosphorylated beta-TP in a lysine-rich domain t hat is not required for specific DNA binding but is implicated in high er order structure formation of telomeres, Therefore, phosphorylation of beta-TP could modulate a function of the telomere protein that is s eparate from specific DNA binding. Phosphoamino acid analysis revealed that the mouse Cdks modify predominantly threonine residues in beta-T P, consistent with the observation that beta-TP contains two consensus Cdk recognition sequences containing threonine residues, In Xenopus e gg extracts that undergo cell cycling, beta-TP was phosphorylated in M phase and dephosphorylated in interphase. This work provides the firs t direct evidence of phosphorylation at telomeres in any organism, as well as indirect evidence for cell cycle regulation of telomere phosph orylation. The Cdc2/cyclin A and Cdc2/cyclin B kinases are required fo r major mitotic events. An attractive model is that phosphorylation of beta-TP by these kinases is required for the breakdown of telomere as sociations with each other and/or with nuclear structures prior to nuc lear division.