DNA-PK and ATM are required for radiation-enhanced integration

Yoshinori Nimura, Sheikh M. Ismail, Akihiro Kurimas, David J. Chen, Craig W. Stevens

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Ionizing radiation is known to improve transfection of exogenous DNA, a process we have termed radiation-enhanced integration. Previous observations have demonstrated that Ku proteins are critical for radiation-enhanced integration. Since Ku proteins form the DNA-binding domain of DNA-PK and since DNA-PK is important in nonhomologous DNA end joining, it was hypothesized that DNA-PK function might be important for radiation-enhanced integration. The ATM protein has been shown to be important in the recognition of a variety of types of DNA damage and to associate with DNA-PK under certain conditions. It was thus hypothesized that ATM might also play a role in radiation-enhanced integration. To test these hypotheses, radiation-enhanced integration was measured in hamster cells that are defective in the catalytic subunit of DNA-PK and in human cells containing mutant ATM. Radiation-enhanced integration was not detected in any of the cell lines with mutant PRKDC (also known as DNA-PKcs), but it was present in cells of the same lineage with wild-type PRKDC. Radiation-enhanced integration was defective in cells lacking kinase activation. ATM-deficient cell lines also showed defective radiation-enhanced integration. These data demonstrate that DNA-PK and ATM must both be active for radiation-enhanced integration to be observed.

Original languageEnglish (US)
Pages (from-to)562-567
Number of pages6
JournalRadiation research
Volume157
Issue number5
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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