Journal article
Molecular steps of G-overhang generation at human telomeres and its function in chromosome end protection
The EMBO journal, Vol.29(16), pp.2788-2801
08/18/2010
Handle:
https://hdl.handle.net/2376/106453
PMCID: PMC2924643
PMID: 20639858
Abstract
Weihang Chai
et al
show that generation of G-strand overhangs, which are important for telomere protection and for promoting telomerase activity, is dynamically regulated during the cell cycle, involving both DNA polymerization and processing mechanisms.
Telomeric G-overhangs are required for the formation of the protective telomere structure and telomerase action. However, the mechanism controlling G-overhang generation at human telomeres is poorly understood. Here, we show that G-overhangs can undergo cell cycle-regulated changes independent of telomerase activity. G-overhangs at lagging telomeres are lengthened in S phase and then shortened in late S/G2 because of C-strand fill-in, whereas the sizes of G-overhangs at leading telomeres remain stable throughout S phase and are lengthened in G2/M. The final nucleotides at measurable C-strands are precisely defined throughout the cell cycle, indicating that C-strand resection is strictly regulated. We demonstrate that C-strand fill-in is mediated by DNA polymerase α (polα) and controlled by cyclin-dependent kinase 1 (CDK1). Inhibition of CDK1 leads to accumulation of lengthened G-overhangs and induces telomeric DNA damage response. Furthermore, depletion of hStn1 results in elongation of G-overhangs and an increase in telomeric DNA damage. Our results suggest that G-overhang generation at human telomeres is regulated by multiple tightly controlled processes and C-strand fill-in is under the control of polα and CDK1.
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Details
- Title
- Molecular steps of G-overhang generation at human telomeres and its function in chromosome end protection
- Creators
- Xueyu Dai - , Spokane, WAChenhui Huang - , Spokane, WAAmruta Bhusari - , Denton, TXShilpa Sampathi - , Spokane, WAKathryn Schubert - , Spokane, WAWeihang Chai - , Spokane, WA
- Publication Details
- The EMBO journal, Vol.29(16), pp.2788-2801
- Academic Unit
- UNKNOWN
- Publisher
- Nature Publishing Group
- Identifiers
- 99900546969201842
- Language
- English
- Resource Type
- Journal article