Home LiteratureArticle Details
PMID: 10535943 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Ku is associated with the telomere in mammals.

Hsu HL, Gilley D, Blackburn EH, Chen DJ

Abstract

Telomeres are specialized DNA/protein complexes that comprise the ends of eukaryotic chromosomes. The highly expressed Ku heterodimer, composed of 70 and 80 K(d) subunits (Ku70 and Ku80), is the high-affinity DNA binding component of the DNA-dependent protein kinase. Ku is critical for nonhomologous DNA double-stranded break repair and site-specific recombination of V(D)J gene segments. Ku also plays an important role in telomere maintenance in yeast. Herein, we report, using an in vivo crosslinking method, that human and hamster telomeric DNAs specifically coimmunoprecipitate with human Ku80 after crosslinking. Localization of Ku to the telomere does not depend on the DNA-dependent protein kinase catalytic component. These findings suggest a direct link between Ku and the telomere in mammalian cells.

MeSH Terms
Animals Antigens, Nuclear CHO Cells Catalytic Domain Cricetinae DNA Helicases DNA-Activated Protein Kinase DNA-Binding Proteins/metabolism Dimerization Humans Ku Autoantigen Nuclear Proteins/metabolism Protein Serine-Threonine Kinases/metabolism Saccharomyces cerevisiae Proteins Telomere Tumor Cells, Cultured
Chemicals
Antigens, Nuclear DNA-Binding Proteins Nuclear Proteins Saccharomyces cerevisiae Proteins high affinity DNA-binding factor, S cerevisiae DNA-Activated Protein Kinase PRKDC protein, human Protein Serine-Threonine Kinases DNA Helicases XRCC5 protein, human Xrcc6 protein, human Ku Autoantigen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hsu H L
Life Sciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
Gilley D
Blackburn E H
Chen D J
References (41)
41 references, click to expand
  1. Length control of human telomeres.
    Cancer J Sci Am. 1998 May;4 Suppl 1:S22-5 PMID: 9619267
  2. Yeast Ku as a regulator of chromosomal DNA end structure.
    Science. 1998 May 1;280(5364):741-4 PMID: 9563951
  3. Effects of Alu insertions on gene function.
    Electrophoresis. 1998 Jun;19(8-9):1260-4 PMID: 9694261
  4. Telomeres and double-strand breaks: trying to make ends meet.
    Trends Cell Biol. 1998 Sep;8(9):339-42 PMID: 9728393
  5. Telomeres--unsticky ends.
    Science. 1998 Sep 18;281(5384):1818-9 PMID: 9776685
  6. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.
    Science. 1998 Nov 20;282(5393):1484-7 PMID: 9822378
  7. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14723-8 PMID: 9843956
  8. Evidence of a differential organization of chromatin containing terminal or interstitial (TTAGGG)n repeats by in situ digestion with nucleases.
    Cytogenet Cell Genet. 1998;82(3-4):195-8 PMID: 9858815
  9. Elongated telomeres in scid mice.
    Genomics. 1999 Mar 1;56(2):221-3 PMID: 10051409
  10. Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening.
    Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3723-8 PMID: 10097104
  11. Mammalian telomeres end in a large duplex loop.
    Cell. 1999 May 14;97(4):503-14 PMID: 10338214
  12. Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast.
    Cell. 1999 May 28;97(5):621-33 PMID: 10367891
  13. Functions of poly(ADP-ribose) polymerase in controlling telomere length and chromosomal stability.
    Nat Genet. 1999 Sep;23(1):76-80 PMID: 10471503
  14. Absence of p350 subunit of DNA-activated protein kinase from a radiosensitive human cell line.
    Science. 1995 Feb 24;267(5201):1183-5 PMID: 7855602
  15. Telomerase activity in normal leukocytes and in hematologic malignancies.
    Blood. 1995 May 1;85(9):2315-20 PMID: 7727765
  16. Telomerase activity in normal and malignant hematopoietic cells.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9082-6 PMID: 7568077
  17. Mapping protein-DNA interactions in vivo with formaldehyde: evidence that histone H4 is retained on a highly transcribed gene.
    Cell. 1988 Jun 17;53(6):937-47 PMID: 2454748
  18. A mutant with a defect in telomere elongation leads to senescence in yeast.
    Cell. 1989 May 19;57(4):633-43 PMID: 2655926
  19. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs.
    Nature. 1990 Mar 8;344(6262):126-32 PMID: 1689810
  20. Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53, and the human Ku autoantigen.
    Mol Cell Biol. 1990 Dec;10(12):6472-81 PMID: 2247067
  21. Transcriptional silencing in yeast is associated with reduced nucleosome acetylation.
    Genes Dev. 1993 Apr;7(4):592-604 PMID: 8458576
  22. Isolation of two cell lines from a human malignant glioma specimen differing in sensitivity to radiation and chemotherapeutic drugs.
    Radiat Res. 1993 Jun;134(3):349-54 PMID: 8316628
  23. Mapping Polycomb-repressed domains in the bithorax complex using in vivo formaldehyde cross-linked chromatin.
    Cell. 1993 Dec 17;75(6):1187-98 PMID: 7903220
  24. Regional assignment of a human DNA repair gene (XRCC5) to 2q35 by X-ray hybrid mapping.
    Genomics. 1994 May 15;21(2):423-7 PMID: 8088837
  25. Disruption of DNA-PK in Ku80 mutant xrs-6 and the implications in DNA double-strand break repair.
    Mutat Res. 1996 Jan 2;362(1):9-19 PMID: 8538653
  26. The DNA-binding protein Hdf1p (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae.
    Nucleic Acids Res. 1996 Feb 15;24(4):582-5 PMID: 8604297
  27. Sequence-specific DNA binding by Ku autoantigen and its effects on transcription.
    Nature. 1996 Mar 21;380(6571):265-8 PMID: 8637578
  28. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination.
    Nature. 1996 Aug 8;382(6591):551-5 PMID: 8700231
  29. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways.
    EMBO J. 1996 Sep 16;15(18):5093-103 PMID: 8890183
  30. Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance.
    Nucleic Acids Res. 1996 Dec 1;24(23):4639-48 PMID: 8972848
  31. DNA double-strand-break sensitivity, DNA replication, and cell cycle arrest phenotypes of Ku-deficient Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):867-72 PMID: 9023348
  32. Sequence-specific DNA binding and transcription factor phosphorylation by Ku Autoantigen/DNA-dependent protein kinase. Phosphorylation of Ser-527 of the rat glucocorticoid receptor.
    J Biol Chem. 1997 Feb 28;272(9):5647-58 PMID: 9038175
  33. Telomerase RNA mutations in Saccharomyces cerevisiae alter telomerase action and reveal nonprocessivity in vivo and in vitro.
    Genes Dev. 1997 Feb 15;11(4):528-40 PMID: 9042865
  34. DNA looping by Ku and the DNA-dependent protein kinase.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4267-72 PMID: 9113978
  35. ATM-dependent telomere loss in aging human diploid fibroblasts and DNA damage lead to the post-translational activation of p53 protein involving poly(ADP-ribose) polymerase.
    EMBO J. 1997 Oct 1;16(19):6018-33 PMID: 9312059
  36. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.
    Cell. 1997 Oct 3;91(1):25-34 PMID: 9335332
  37. Growth retardation and leaky SCID phenotype of Ku70-deficient mice.
    Immunity. 1997 Nov;7(5):653-65 PMID: 9390689
  38. Extension of life-span by introduction of telomerase into normal human cells.
    Science. 1998 Jan 16;279(5349):349-52 PMID: 9454332
  39. The telomere and telomerase: nucleic acid-protein complexes acting in a telomere homeostasis system. A review.
    Biochemistry (Mosc). 1997 Nov;62(11):1196-201 PMID: 9467842
  40. Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing.
    EMBO J. 1998 Mar 16;17(6):1819-28 PMID: 9501103
  41. Telomerase in cancer: diagnostic, prognostic, and therapeutic implications.
    Cancer J Sci Am. 1998 May;4 Suppl 1:S26-34 PMID: 9619268
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1999-10-26
Pages
12454-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22947
Subset
IM
Grants
NIGMS NIH HHS · GM26259 · United States
NCI NIH HHS · R37 CA050519 · United States
NIGMS NIH HHS · R01 GM026259 · United States
NCI NIH HHS · CA50519 · United States
NIGMS NIH HHS · R37 GM026259 · United States
NCI NIH HHS · R01 CA050519 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]