A Positive Role for the Ku Complex in DNA Replication Following Strand Break Damage in Mammals

Su Jung Park, Samantha L M Ciccone, Brian Freie, Akihiro Kurimasa, David J. Chen, Gloria C. Li, D. Wade Clapp, Suk Hee Lee

Research output: Contribution to journalArticle

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Abstract

Ku70-Ku80 complex is the regulatory subunit of DNA-dependent protein kinase (DNA-PK) and plays an essential role in double-strand break repair following ionizing radiation (IR). It preferentially interacts with chromosomal breaks and protects DNA ends from nuclease attack. Here we show evidence that cells defective in Ku80 exhibit a significantly slow S phase progression following DNA damage. IR-induced retardation in S phase progression in Ku80-/- cells was not due to the lack of DNA-PK kinase activity because both wild-type cells and DNA-PKcs-deficient cells showed no such symptom. Instead, proliferating cell nuclear antigen (PCNA) dissociated from chromosomes following IR in Ku80-deficient cells but not in wild-type or DNA-PKcs-deficient cells. Treatment of HeLa cells with IR induced colocalization of the Ku complex with PCNA on chromosomes. Together, these results suggest that binding of the Ku complex at chromosomal breaks may be necessary to maintain the sliding clamps (PCNA) on chromatin, which would allow cells to resume DNA replication without a major delay following IR.

Original languageEnglish (US)
Pages (from-to)6046-6055
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number7
DOIs
StatePublished - Feb 13 2004

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Mammals
Ionizing radiation
DNA Replication
Ionizing Radiation
Proliferating Cell Nuclear Antigen
DNA-Activated Protein Kinase
DNA
Chromosomes
Chromosome Breakage
S Phase
Clamping devices
Chromatin
Deoxyribonucleases
Repair
Phosphotransferases
HeLa Cells
DNA Damage

ASJC Scopus subject areas

  • Biochemistry

Cite this

Park, S. J., Ciccone, S. L. M., Freie, B., Kurimasa, A., Chen, D. J., Li, G. C., ... Lee, S. H. (2004). A Positive Role for the Ku Complex in DNA Replication Following Strand Break Damage in Mammals. Journal of Biological Chemistry, 279(7), 6046-6055. https://doi.org/10.1074/jbc.M311054200

A Positive Role for the Ku Complex in DNA Replication Following Strand Break Damage in Mammals. / Park, Su Jung; Ciccone, Samantha L M; Freie, Brian; Kurimasa, Akihiro; Chen, David J.; Li, Gloria C.; Clapp, D. Wade; Lee, Suk Hee.

In: Journal of Biological Chemistry, Vol. 279, No. 7, 13.02.2004, p. 6046-6055.

Research output: Contribution to journalArticle

Park, SJ, Ciccone, SLM, Freie, B, Kurimasa, A, Chen, DJ, Li, GC, Clapp, DW & Lee, SH 2004, 'A Positive Role for the Ku Complex in DNA Replication Following Strand Break Damage in Mammals', Journal of Biological Chemistry, vol. 279, no. 7, pp. 6046-6055. https://doi.org/10.1074/jbc.M311054200
Park, Su Jung ; Ciccone, Samantha L M ; Freie, Brian ; Kurimasa, Akihiro ; Chen, David J. ; Li, Gloria C. ; Clapp, D. Wade ; Lee, Suk Hee. / A Positive Role for the Ku Complex in DNA Replication Following Strand Break Damage in Mammals. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 7. pp. 6046-6055.
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