Phosphorylation of the Oxytricha telomere protein: possible cell cycle regulation.
In the macronucleus of the ciliate Oxytricha nova, telomeres end with single-stranded (T4G4)2 DNA bound to a heterodimeric telomere protein (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-dependent kinases (Cdks) phosphorylated beta-TP in a lysine-rich domain that is not required for specific DNA binding but is implicated in higher order structure formation of telomeres. Therefore, phosphorylation of beta-TP could modulate a function of the telomere protein that is separate from specific DNA binding. Phosphoamino acid analysis revealed that the mouse Cdks modify predominantly threonine residues in beta-TP, consistent with the observation that beta-TP contains two consensus Cdk recognition sequences containing threonine residues. In Xenopus egg extracts that undergo cell cycling, beta-TP was phosphorylated in M phase and dephosphorylated in interphase. This work provides the first direct evidence of phosphorylation at telomeres in any organism, as well as indirect evidence for cell cycle regulation of telomere phosphorylation. The Cdc2/cyclin A and Cdc2/cyclin B kinases are required for major mitotic events. An attractive model is that phosphorylation of beta-TP by these kinases is required for the breakdown of telomere associations with each other and/or with nuclear structures prior to nuclear division.
Hicke
B
B
Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado, Boulder 80309-0215, USA.
Rempel
R
R
Maller
J
J
Swank
R A
RA
Hamaguchi
J R
JR
Bradbury
E M
EM
Prescott
D M
DM
Cech
T R
TR
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D004277:DNA, Single-Stranded / Q000378:metabolism; D008969:Molecular Sequence Data; D016813:Oxytricha / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry; D016615:Telomere / Q000378:metabolism*
D004277:DNA, Single-Stranded; D011506:Proteins