Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells
Open accessAbstract
DNA repair by nonhomologous end-joining (NHEJ) relies on the Ku70:Ku80 heterodimer in species ranging from yeast to man. In Saccharomyces cerevisiae and Schizosaccharomyces pombe, Ku also controls telomere functions. Here, we show that Ku70, Ku80, and DNA-PKcs, with which Ku interacts, associate in vivo with telomeric DNA in several human cell types, and we show that these associations are not significantly affected by DNA-damaging agents. We also demonstrate that inactivation of Ku80 or Ku70 in the mouse yields telomeric shortening in various primary cell types at different developmental stages. By contrast, telomere length is not altered in cells impaired in XRCC4 or DNA ligase IV, two other NHEJ components. We also observe higher genomic instability in Ku-deficient cells than in XRCC4-null cells. This suggests that chromosomal instability of Ku-deficient cells results from a combination of compromised telomere stability and defective NHEJ.
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At least three core NHEJ factors, namely Ku70, Ku80, and DNA-PKcs, localize to telomeres.
“at least three core NHEJ factors, namely Ku70, Ku80, and DNA-PKcs, localize to telomeres (d'Adda di Fagagna et al., 2001”
From DNA Repair, Genome Stability, and Aging (2005) · cites this paper as d'Adda di Fagagna et al., 2001
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- Authors
- d'Adda di Fagagna, F., Hande, M. P., Tong, W.-M., Roth, D., Lansdorp, P. M., Wang, Z.-Q., & Jackson, S. P.
- Affiliations
- BC Cancer Agency (CA)
- Centre international de recherche sur le cancer (FR)
- Howard Hughes Medical Institute (US)
- University of Cambridge (GB)
- Corresponding author
- Jackson, Stephen P.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 11
- Issue
- 15
- Pages
- 1192-1196
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2047804529
- Cited by
- 293
- References
- 26
- Citations by year
- 2025: 6 · 2024: 5 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 11 · 2013: 8 · 2012: 7
- FWCI
- 20.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- non-homologous end joining, Ku70, Ku80, DNA-PKcs, telomere length, telomere shortening, chromosomal instability, genomic instability, XRCC4, DNA ligase IV, DNA repair
- MeSH terms
- Ku Autoantigen, Animals, Chromosomes, DNA, DNA Repair, DNA Helicases, DNA-Binding Proteins, Mice, Mutant Strains, Nuclear Proteins, Telomere, Protein Serine-Threonine Kinases, In Situ Hybridization, Fluorescence, Saccharomyces cerevisiae Proteins, Antigens, Nuclear, Mice, DNA-Activated Protein Kinase
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