CDK1 differentially regulates G-overhang generation at leading- and lagging-strand telomeres in telomerase-negative cells in G2 phase

Xueyu Dai; Chenhui Huang; Weihang Chai

doi:10.4161/cc.21472

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CDK1 differentially regulates G-overhang generation at leading- and lagging-strand telomeres in telomerase-negative cells in G2 phase

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CDK1 differentially regulates G-overhang generation at leading- and lagging-strand telomeres in telomerase-negative cells in G2 phase

Xueyu Dai, Chenhui Huang and Weihang Chai

Cell cycle (Georgetown, Tex.), Vol.11(16), pp.3079-3086

08/15/2012

DOI: https://doi.org/10.4161/cc.21472

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https://hdl.handle.net/2376/111046

PMCID: PMC3442918

PMID: 22871736

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Abstract

CDC2 Protein Kinase - antagonists & inhibitors

Humans

Enzyme Inhibitors - pharmacology

DNA Replication

DNA - metabolism

2-Aminopurine - pharmacology

Quinolines - pharmacology

CDC2 Protein Kinase - metabolism

DNA - genetics

Flow Cytometry

Telomerase - genetics

Chromatin Immunoprecipitation

2-Aminopurine - analogs & derivatives

G2 Phase

Telomerase - metabolism

Telomere - metabolism

Thiazoles - pharmacology

Enzyme Activation

HeLa Cells

Telomere-Binding Proteins - metabolism

DNA Polymerase I - metabolism

Human telomeres contain single-stranded 3' G-overhangs that function in telomere end protection and telomerase action. Previously we have demonstrated that multiple steps involving C-strand end resection, telomerase elongation and C-strand fill-in contribute to G-overhang generation in telomerase-positive cancer cells. However, how G-overhangs are generated in telomerase-negative human somatic cells is unknown. Here, we report that C-strand fill-in is present at lagging-strand telomeres in telomerase-negative human cells but not at leading-strand telomeres, suggesting that C-strand fill-in is independent of telomerase extension of G-strand. We further show that while cyclin-dependent kinase 1 (CDK1) positively regulates C-strand fill-in, CDK1 unlikely regulates G-overhang generation at leading-strand telomeres. In addition, DNA polymerase α (Polα) association with telomeres is not altered upon CDK1 inhibition, suggesting that CDK1 does not control the loading of Polα to telomeres during fill-in. In summary, our results reveal that G-overhang generation at leading- and lagging-strand telomeres are regulated by distinct mechanisms in human cells.

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Title: CDK1 differentially regulates G-overhang generation at leading- and lagging-strand telomeres in telomerase-negative cells in G2 phase
Creators: Xueyu Dai - School of Molecular Biosciences, Washington State University, Spokane, WA, USA
Chenhui Huang
Weihang Chai
Publication Details: Cell cycle (Georgetown, Tex.), Vol.11(16), pp.3079-3086
Academic Unit: UNKNOWN
Publisher: United States
Grant note: R15GM099008 / NIGMS NIH HHS R21 AG041375 / NIA NIH HHS R15 GM099008 / NIGMS NIH HHS
Identifiers: 99900547352301842
Language: English
Resource Type: Journal article