Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86

Kyungjae Myung, Goutam Ghosh, Farjana J. Fattah, Gang Li, Haeyoung Kim, Amalia Dutia, Evgenia Pak, Stephanie Smith, Eric A. Hendrickson

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Ku86 plays a key role in nonhomologous end joining in organisms as evolutionarily disparate as bacteria and humans. In eukaryotic cells, Ku86 has also been implicated in the regulation of telomere length although the effect of Ku86 mutations varies considerably between species. Indeed, telomeres either shorten significantly, shorten slightly, remain unchanged, or lengthen significantly in budding yeast, fission yeast, chicken cells, or plants, respectively, that are null for Ku86 expression. Thus, it has been unclear which model system is most relevant for humans. We demonstrate here that the functional inactivation of even a single allele of Ku86 in human somatic cells results in profound telomere loss, which is accompanied by an increase in chromosomal fusions, translocations, and genomic instability. Together, these experiments demonstrate that Ku86, separate from its role in nonhomologous end joining, performs the additional function in human somatic cells of suppressing genomic instability through the regulation of telomere length.

Original languageEnglish (US)
Pages (from-to)5050-5059
Number of pages10
JournalMolecular and cellular biology
Volume24
Issue number11
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

Fingerprint

Genomic Instability
Telomere
Telomere Shortening
Genetic Translocation
Saccharomycetales
Schizosaccharomyces
Plant Cells
Eukaryotic Cells
Chickens
Alleles
Bacteria
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. / Myung, Kyungjae; Ghosh, Goutam; Fattah, Farjana J.; Li, Gang; Kim, Haeyoung; Dutia, Amalia; Pak, Evgenia; Smith, Stephanie; Hendrickson, Eric A.

In: Molecular and cellular biology, Vol. 24, No. 11, 01.06.2004, p. 5050-5059.

Research output: Contribution to journalArticle

Myung, Kyungjae ; Ghosh, Goutam ; Fattah, Farjana J. ; Li, Gang ; Kim, Haeyoung ; Dutia, Amalia ; Pak, Evgenia ; Smith, Stephanie ; Hendrickson, Eric A. / Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86. In: Molecular and cellular biology. 2004 ; Vol. 24, No. 11. pp. 5050-5059.
@article{ed712c14d14e495bb07e397b02110973,
title = "Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86",
abstract = "Ku86 plays a key role in nonhomologous end joining in organisms as evolutionarily disparate as bacteria and humans. In eukaryotic cells, Ku86 has also been implicated in the regulation of telomere length although the effect of Ku86 mutations varies considerably between species. Indeed, telomeres either shorten significantly, shorten slightly, remain unchanged, or lengthen significantly in budding yeast, fission yeast, chicken cells, or plants, respectively, that are null for Ku86 expression. Thus, it has been unclear which model system is most relevant for humans. We demonstrate here that the functional inactivation of even a single allele of Ku86 in human somatic cells results in profound telomere loss, which is accompanied by an increase in chromosomal fusions, translocations, and genomic instability. Together, these experiments demonstrate that Ku86, separate from its role in nonhomologous end joining, performs the additional function in human somatic cells of suppressing genomic instability through the regulation of telomere length.",
author = "Kyungjae Myung and Goutam Ghosh and Fattah, {Farjana J.} and Gang Li and Haeyoung Kim and Amalia Dutia and Evgenia Pak and Stephanie Smith and Hendrickson, {Eric A.}",
year = "2004",
month = "6",
day = "1",
doi = "10.1128/MCB.24.11.5050-5059.2004",
language = "English (US)",
volume = "24",
pages = "5050--5059",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Regulation of telomere length and suppression of genomic instability in human somatic cells by Ku86

AU - Myung, Kyungjae

AU - Ghosh, Goutam

AU - Fattah, Farjana J.

AU - Li, Gang

AU - Kim, Haeyoung

AU - Dutia, Amalia

AU - Pak, Evgenia

AU - Smith, Stephanie

AU - Hendrickson, Eric A.

PY - 2004/6/1

Y1 - 2004/6/1

N2 - Ku86 plays a key role in nonhomologous end joining in organisms as evolutionarily disparate as bacteria and humans. In eukaryotic cells, Ku86 has also been implicated in the regulation of telomere length although the effect of Ku86 mutations varies considerably between species. Indeed, telomeres either shorten significantly, shorten slightly, remain unchanged, or lengthen significantly in budding yeast, fission yeast, chicken cells, or plants, respectively, that are null for Ku86 expression. Thus, it has been unclear which model system is most relevant for humans. We demonstrate here that the functional inactivation of even a single allele of Ku86 in human somatic cells results in profound telomere loss, which is accompanied by an increase in chromosomal fusions, translocations, and genomic instability. Together, these experiments demonstrate that Ku86, separate from its role in nonhomologous end joining, performs the additional function in human somatic cells of suppressing genomic instability through the regulation of telomere length.

AB - Ku86 plays a key role in nonhomologous end joining in organisms as evolutionarily disparate as bacteria and humans. In eukaryotic cells, Ku86 has also been implicated in the regulation of telomere length although the effect of Ku86 mutations varies considerably between species. Indeed, telomeres either shorten significantly, shorten slightly, remain unchanged, or lengthen significantly in budding yeast, fission yeast, chicken cells, or plants, respectively, that are null for Ku86 expression. Thus, it has been unclear which model system is most relevant for humans. We demonstrate here that the functional inactivation of even a single allele of Ku86 in human somatic cells results in profound telomere loss, which is accompanied by an increase in chromosomal fusions, translocations, and genomic instability. Together, these experiments demonstrate that Ku86, separate from its role in nonhomologous end joining, performs the additional function in human somatic cells of suppressing genomic instability through the regulation of telomere length.

UR - http://www.scopus.com/inward/record.url?scp=2442688032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442688032&partnerID=8YFLogxK

U2 - 10.1128/MCB.24.11.5050-5059.2004

DO - 10.1128/MCB.24.11.5050-5059.2004

M3 - Article

C2 - 15143195

AN - SCOPUS:2442688032

VL - 24

SP - 5050

EP - 5059

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 11

ER -