Regulation of Telomere Elongation by the Cyclin-Dependent Kinase CDK1

Christopher J. Frank, Molly Hyde, Carol W Greider

Research output: Contribution to journalArticle

Abstract

Telomere elongation is cell-cycle regulated and requires the coordinated activity of proteins involved in the DNA damage response. We used an assay that detects de novo telomere addition to examine the role of the cyclin-dependent kinase Cdk1 (Cdc28) in cell-cycle-specific telomere elongation. Inhibition of an ATP analog-sensitive allele of Cdk1 completely blocked the addition of telomere repeats. Mutations in Rif2 and DNA polymerase α that cause increased telomere elongation were unable to compensate for the loss of Cdk1 activity, suggesting Cdk1 activity is required for an early step in telomere addition. Mutations in DNA repair proteins that act with Cdk1 at double-strand breaks also prevented telomere elongation. Cdk1 activity was required for the generation of 3′ single-strand overhangs at both native and de novo telomeres. We propose Cdk1 activity controls the timing of telomere elongation by regulating the single-strand overhang at chromosome ends.

Original languageEnglish (US)
Pages (from-to)423-432
Number of pages10
JournalMolecular Cell
Volume24
Issue number3
DOIs
StatePublished - Nov 3 2006

Fingerprint

Cyclin-Dependent Kinases
Telomere
Cell Cycle
Mutation
DNA-Directed DNA Polymerase
DNA Repair
DNA Damage
Proteins
Chromosomes
Adenosine Triphosphate
Alleles

Keywords

  • CELLCYCLE
  • DNA

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Regulation of Telomere Elongation by the Cyclin-Dependent Kinase CDK1. / Frank, Christopher J.; Hyde, Molly; Greider, Carol W.

In: Molecular Cell, Vol. 24, No. 3, 03.11.2006, p. 423-432.

Research output: Contribution to journalArticle

Frank, Christopher J. ; Hyde, Molly ; Greider, Carol W. / Regulation of Telomere Elongation by the Cyclin-Dependent Kinase CDK1. In: Molecular Cell. 2006 ; Vol. 24, No. 3. pp. 423-432.
@article{2688b9fa4e0c44ea83d97a76d1313a4f,
title = "Regulation of Telomere Elongation by the Cyclin-Dependent Kinase CDK1",
abstract = "Telomere elongation is cell-cycle regulated and requires the coordinated activity of proteins involved in the DNA damage response. We used an assay that detects de novo telomere addition to examine the role of the cyclin-dependent kinase Cdk1 (Cdc28) in cell-cycle-specific telomere elongation. Inhibition of an ATP analog-sensitive allele of Cdk1 completely blocked the addition of telomere repeats. Mutations in Rif2 and DNA polymerase α that cause increased telomere elongation were unable to compensate for the loss of Cdk1 activity, suggesting Cdk1 activity is required for an early step in telomere addition. Mutations in DNA repair proteins that act with Cdk1 at double-strand breaks also prevented telomere elongation. Cdk1 activity was required for the generation of 3′ single-strand overhangs at both native and de novo telomeres. We propose Cdk1 activity controls the timing of telomere elongation by regulating the single-strand overhang at chromosome ends.",
keywords = "CELLCYCLE, DNA",
author = "Frank, {Christopher J.} and Molly Hyde and Greider, {Carol W}",
year = "2006",
month = "11",
day = "3",
doi = "10.1016/j.molcel.2006.10.020",
language = "English (US)",
volume = "24",
pages = "423--432",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Regulation of Telomere Elongation by the Cyclin-Dependent Kinase CDK1

AU - Frank, Christopher J.

AU - Hyde, Molly

AU - Greider, Carol W

PY - 2006/11/3

Y1 - 2006/11/3

N2 - Telomere elongation is cell-cycle regulated and requires the coordinated activity of proteins involved in the DNA damage response. We used an assay that detects de novo telomere addition to examine the role of the cyclin-dependent kinase Cdk1 (Cdc28) in cell-cycle-specific telomere elongation. Inhibition of an ATP analog-sensitive allele of Cdk1 completely blocked the addition of telomere repeats. Mutations in Rif2 and DNA polymerase α that cause increased telomere elongation were unable to compensate for the loss of Cdk1 activity, suggesting Cdk1 activity is required for an early step in telomere addition. Mutations in DNA repair proteins that act with Cdk1 at double-strand breaks also prevented telomere elongation. Cdk1 activity was required for the generation of 3′ single-strand overhangs at both native and de novo telomeres. We propose Cdk1 activity controls the timing of telomere elongation by regulating the single-strand overhang at chromosome ends.

AB - Telomere elongation is cell-cycle regulated and requires the coordinated activity of proteins involved in the DNA damage response. We used an assay that detects de novo telomere addition to examine the role of the cyclin-dependent kinase Cdk1 (Cdc28) in cell-cycle-specific telomere elongation. Inhibition of an ATP analog-sensitive allele of Cdk1 completely blocked the addition of telomere repeats. Mutations in Rif2 and DNA polymerase α that cause increased telomere elongation were unable to compensate for the loss of Cdk1 activity, suggesting Cdk1 activity is required for an early step in telomere addition. Mutations in DNA repair proteins that act with Cdk1 at double-strand breaks also prevented telomere elongation. Cdk1 activity was required for the generation of 3′ single-strand overhangs at both native and de novo telomeres. We propose Cdk1 activity controls the timing of telomere elongation by regulating the single-strand overhang at chromosome ends.

KW - CELLCYCLE

KW - DNA

UR - http://www.scopus.com/inward/record.url?scp=33750431337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750431337&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2006.10.020

DO - 10.1016/j.molcel.2006.10.020

M3 - Article

C2 - 17070718

AN - SCOPUS:33750431337

VL - 24

SP - 423

EP - 432

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 3

ER -