J Cancer 2013; 4(8):606-613. doi:10.7150/jca.6453 This issue Cite

Research Paper

Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype

Seow Fong Yap, Cynthia SK Boo, Susan LE Loong, Rajamanickam Baskar

Department of Radiation Oncology, Division of Cellular and Molecular Research, National Cancer Centre, Singapore.

Citation:
Yap SF, Boo CSK, Loong SLE, Baskar R. Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype. J Cancer 2013; 4(8):606-613. doi:10.7150/jca.6453. https://www.jcancer.org/v04p0606.htm
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Abstract

Background: Non-homologous end joining (NHEJ) is the main repair pathway for DNA double strand breaks (DSBs) induced by ionizing radiation in mammalian cells. Subsets of cancer patients are hypersensitive to radiotherapy after standard doses. We sought to determine the radiosensitivity of human lymphoblastic cells (LB0005) for the abnormality in NHEJ components.

Methods: Lymphoblastic (LB0005) cells are derived from an adult cancer patient with late radionecrosis. A low magnesium in vitro DNA-end joining assay was performed to examine for any defect in NHEJ activity. Single-nucleotide polymorphism (SNP) and sequence analysis were performed to examine for abnormality if any, in the genetic sequence of known NHEJ components.

Results: LB0005 cells showed a gain of functional abnormality in the NHEJ pathway. While genetic sequence analysis showed no apparent mutational variations in the known classical NHEJ components, DNA-PKcs (DNA-dependent protein kinase catalytic subunit) protein is reduced in quantity compared to normal control, in spite of higher transcript levels.

Conclusions: Taken together cells derived from a radiosensitive patient showed an abnormality in NHEJ activity. Proteins other than the classical NHEJ factors may regulate the NHEJ activity. Furthermore, the defect in theses regulatory proteins may have an impact on the stability of DNA-PKcs.

Keywords: DNA-PKcs, Non-homologous end joining, NHEJ


Citation styles

APA
Yap, S.F., Boo, C.SK., Loong, S.LE., Baskar, R. (2013). Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype. Journal of Cancer, 4(8), 606-613. https://doi.org/10.7150/jca.6453.

ACS
Yap, S.F.; Boo, C.SK.; Loong, S.LE.; Baskar, R. Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype. J. Cancer 2013, 4 (8), 606-613. DOI: 10.7150/jca.6453.

NLM
Yap SF, Boo CSK, Loong SLE, Baskar R. Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype. J Cancer 2013; 4(8):606-613. doi:10.7150/jca.6453. https://www.jcancer.org/v04p0606.htm

CSE
Yap SF, Boo CSK, Loong SLE, Baskar R. 2013. Normal Sequence and Activity but Reduced Levels of DNA-Pkcs in Human Lymphoblastic Cells Implicate Impaired Protein Stability with Radiosensitive Phenotype. J Cancer. 4(8):606-613.

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