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PMID: 11256607 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang.

EMBO reports ·Vol. 1 ·No. 3 ·2000-09-00 ·Pages 244-52

Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, Blasco MA

Abstract

Ku86 together with Ku70, DNA-PKcs, XRCC4 and DNA ligase IV forms a complex involved in repairing DNA double-strand breaks (DSB) in mammals. Yeast Ku has an essential role at the telomere; in particular, Ku deficiency leads to telomere shortening, loss of telomere clustering, loss of telomeric silencing and deregulation of the telomeric G-overhang. In mammals, Ku proteins associate to telomeric repeats; however, the possible role of Ku in regulating telomere length has not yet been addressed. We have measured telomere length in different cell types from wild-type and Ku86-deficient mice. In contrast to yeast, Ku86 deficiency does not result in telomere shortening or deregulation of the G-strand overhang. Interestingly, Ku86-/- cells show telomeric fusions with long telomeres (>81 kb) at the fusion point. These results indicate that mammalian Ku86 plays a fundamental role at the telomere by preventing telomeric fusions independently of the length of TTAGGG repeats and the integrity of the G-strand overhang.

MeSH Terms
Animals Antigens, Nuclear Bone Marrow Cells Cells, Cultured Chromosome Aberrations/genetics DNA Damage/genetics DNA Helicases DNA-Binding Proteins/deficiency,genetics,metabolism Female Fibroblasts Flow Cytometry Gene Deletion Germ Cells In Situ Hybridization, Fluorescence Ku Autoantigen Male Mice Mice, Knockout Nuclear Proteins/deficiency,genetics,metabolism Recombination, Genetic/genetics Repetitive Sequences, Nucleic Acid/genetics Saccharomyces cerevisiae Proteins Single-Strand Specific DNA and RNA Endonucleases/metabolism Spleen/cytology Telomerase/metabolism Telomere/chemistry,genetics,metabolism
Chemicals
Antigens, Nuclear DNA-Binding Proteins Nuclear Proteins Saccharomyces cerevisiae Proteins high affinity DNA-binding factor, S cerevisiae Telomerase Single-Strand Specific DNA and RNA Endonucleases DNA Helicases XRCC5 protein, human Xrcc5 protein, mouse Xrcc6 protein, human Xrcc6 protein, mouse Ku Autoantigen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Samper E
Department of Immunology and Oncology, Centro National de Biotecnología, Spain.
Goytisolo F A
Slijepcevic P
van Buul P P
Blasco M A
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1093/embo-reports/kvd051
Published
2000-09-00
Pages
244-52
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1083725
Subset
IM
External Links
PubMed source DOI: 10.1093/embo-reports/kvd051 PMC Full Text View journal details
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