A positive role for the Ku complex in DNA replication following strand break damage in mammals Journal Article
| Authors: | Park, S. J.; Ciccone, S. L. M.; Freie, B.; Kurimasa, A.; Chen, D. J.; Li, G. C.; Clapp, D. W.; Lee, S. H. |
| Article Title: | A positive role for the Ku complex in DNA replication following strand break damage in mammals |
| 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. |
| Keywords: | controlled study; unclassified drug; human cell; dna-binding proteins; nonhuman; dna replication; protein localization; animal cell; chromosome; mouse; mammalia; animals; mice; dna damage; cell cycle; cell cycle s phase; dna repair; microscopy, confocal; embryo; protein binding; enzyme activity; hela cell; hela cells; time factors; dose-response relationship, radiation; animalia; dna strand breakage; dna; antigens; chromatin; ionizing radiation; radiation, ionizing; chromosome breakage; nuclease; dimerization; cell nucleus; cycline; ku antigen; biochemistry; dissociation; enzymes; dna helicases; cytosol; chromosomes; complexation; bromodeoxyuridine; proliferating cell nuclear antigen; dna dependent protein kinase; antigens, nuclear; kurchatovium; protein ku80; humans; human; priority journal; article; proliferating cell nuclear antigen (pcna); chromatins |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 279 |
| Issue: | 7 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2004-02-13 |
| Start Page: | 6046 |
| End Page: | 6055 |
| Language: | English |
| DOI: | 10.1074/jbc.M311054200 |
| PROVIDER: | scopus |
| PUBMED: | 14617623 |
| DOI/URL: | |
| Notes: | J. Biol. Chem. -- Cited By (since 1996):22 -- Export Date: 16 June 2014 -- CODEN: JBCHA -- Source: Scopus |
