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001-es BibID:BIBFORM047646
035-os BibID:PMID:16298690
Első szerző:Bácsi Attila (immunológus)
Cím:Modulation of DNA-dependent protein kinase activity in chlorambucil-treated cells / Attila Bacsi, Subbaraj Kannan, Myung-Soog Lee, Tapas K. Hazra, Istvan Boldogh
Dátum:2005
ISSN:0891-5849
Megjegyzések:DNA-dependent protein kinase (DNA-PK) is activated in a two-step process whereby the Ku heterodimer first binds to the DNA double-strandbreaks (dsbs) and then the DNA-PK catalytic subunit (cs) is recruited to form a repair complex. Oxidative stress is simultaneously generated alongwith DNA damage by ionizing radiation or chemotherapeutic agents whose impact on the DNA-PK activity has not previously been investigated.Here we show that the DNA damage-induced kinase activity of DNA-PK was modulated by oxidative stress, which was induced along with DNAdsbs in chlorambucil (Cbl)-exposed cells. Pretreatment with the antioxidants, 2(3)-t-butyl-4-hydroxyanisole or N-acetyl-l-cysteine enhanced theamount of DNA-PKcs phosphorylated at threonine 2609 (DNA-PKpThr2609) at the DNA dsbs and DNA-PK activity. Conversely, oxidative stressinduced by l-buthionine (SR)-sulfoximine or glucose oxidase decreased the DNA-PK activity in Cbl-exposed cells. In addition, DNA-PKpThr2609was poorly detectable at the site of DNA dsbs, as shown by colocalization to DNA-end-binding pH2AX or p53BP1. There was no change in theprotein levels of DNA-PKcs, Ku70, or Ku86. Data from these studies provide the first evidence that oxidative stress effects posttranslationalmodification and assembly of DNA-PK complex at DNA dsbs, and thereby repair of DNA dsbs.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Oxidative stress
DNA-PK
DNA dsbs repair
Free radicals
Megjelenés:Free Radical Biology and Medicine. - 39 : 12 (2005), p. 1650-1659. -
További szerzők:Kannan, Subbaraj Myung-Soog, Lee Hazra, Tapas K. Boldogh István
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