Journal article
Timeless preserves telomere length by promoting efficient DNA replication through human telomeres
Cell cycle (Georgetown, Tex.), v 11(12), pp 2337-2347
15 Jun 2012
PMID: 22672906
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A variety of telomere protection programs are utilized to preserve telomere structure. However, the complex nature of telomere maintenance remains elusive. The Timeless protein associates with the replication fork and is thought to support efficient progression of the replication fork through natural impediments, including replication fork block sites. However, the mechanism by which Timeless regulates such genomic regions is not understood. Here, we report the role of Timeless in telomere length maintenance. We demonstrate that Timeless depletion leads to telomere shortening in human cells. This length maintenance is independent of telomerase, and Timeless depletion causes increased levels of DNA damage, leading to telomere aberrations. We also show that Timeless is associated with Shelterin components TRF1 and TRF2. Timeless depletion slows telomere replication in vitro, and Timeless-depleted cells fail to maintain TRF1-mediated accumulation of replisome components at telomeric regions. Furthermore, telomere replication undergoes a dramatic delay in Timeless-depleted cells. These results suggest that Timeless functions together with TRF1 to prevent fork collapse at telomere repeat DNA and ensure stable maintenance of telomere length and integrity.
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Details
- Title
- Timeless preserves telomere length by promoting efficient DNA replication through human telomeres
- Creators
- Adam R Leman - Department of Biochemistry and Molecular Biology; Drexel University College of Medicine; Philadelphia, PA USAJayaraju Dheekollu - The Wistar Institute; Philadelphia, PA USAZhong Deng - The Wistar Institute; Philadelphia, PA USASeung Woo Lee - Department of Biochemistry and Molecular Biology; Drexel University College of Medicine; Philadelphia, PA USAMukund M Das - Department of Biochemistry and Molecular Biology; Drexel University College of Medicine; Philadelphia, PA USAPaul M Lieberman - The Wistar Institute; Philadelphia, PA USAEishi Noguchi - Department of Biochemistry and Molecular Biology; Drexel University College of Medicine; Philadelphia, PA USA
- Publication Details
- Cell cycle (Georgetown, Tex.), v 11(12), pp 2337-2347
- Publisher
- Landes Bioscience
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000305353000022
- Scopus ID
- 2-s2.0-84862872436
- Other Identifier
- 991014877992204721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology