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Processing of clustered DNA damage in human breast cancer cells MCF-7 with partial DNA-PKcs deficiency.
Peddi, Prakash; Francisco, Dave C; Cecil, Angela M; Hair, Jessica M; Panayiotidis, Mihalis I; Georgakilas, Alexandros G.
Afiliação
  • Peddi P; Department of Biology, Thomas Harriot College of Arts and Sciences, East Carolina University, Howell Science Complex, Greenville, NC 27858, USA.
Cancer Lett ; 269(1): 174-83, 2008 Sep 28.
Article em En | MEDLINE | ID: mdl-18550272
Complex DNA damage such as double strand breaks (DSBs) and non-DSB bistranded oxidative clustered DNA lesions (OCDL) (two or more DNA lesions within a short DNA fragment of 1-10bp on opposing DNA strands) are considered the hallmark of ionizing radiation. Clustered DNA lesions are hypothesized to be repair-resistant lesions challenging the repair mechanisms of the cell. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) plays an important role during the processing of DSBs. To evaluate the role of DNA-PKcs in the processing of complex DNA damage in human MCF-7 breast cancer cells we used small interfering RNAs (siRNAs) to target the silencing of the gene Prkdc coding for DNA-PKcs. MCF-7 cells with knockdown DNA-PKcs expression showed a marked decrease in their efficiency to process DSBs and OCDL after exposure to radiotherapy-relevant gamma ray doses. For the detection and measurement of complex DSBs and OCDL, we used the gamma-H2AX assay and an adaptation of pulsed field gel electrophoresis with Escherichia coli repair enzymes as DNA damage probes. An accumulation of all types of DNA damage was detected for the siRNA-treated MCF-7 cells compared to controls. These findings point to the important role of DNA-PKcs in the processing of complex DNA damage and its potential association with breast cancer development.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Neoplasias da Mama / Proteína Quinase Ativada por DNA Tipo de estudo: Etiology_studies Limite: Female / Humans Idioma: En Revista: Cancer Lett Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Irlanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Neoplasias da Mama / Proteína Quinase Ativada por DNA Tipo de estudo: Etiology_studies Limite: Female / Humans Idioma: En Revista: Cancer Lett Ano de publicação: 2008 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Irlanda