Endogenous Factors Causative of Spontaneous DNA Damage that Leads to Random Integration in Human Cells

Haruna Kamekawa

doi:10.4172/2329-6682.1000105

Random integration is a phenomenon in which transfected DNA molecules integrate into (random sites of) the host genome via non-homologous recombination. Although it is assumed that repair of DNA double-strand breaks leads to random integration events, how these endogenous DNA lesions are generated in living cells is poorly understood. In this study, we present evidence that DNA topoisomerase IIa (Top2α) and reactive oxygen species (ROS) are responsible for causing genomic DNA damage that leads to random integration. Specifically, we employed a human pre-B lymphocyte cell line to examine the effects of cellular Top2 expression levels and oxygen concentrations during cell culture. We find that treating cells with Top2α siRNA significantly reduces random integration frequency, while the absence of Top2β had little or no impact. We also show that cells continuously cultured under low (3%) oxygen culture conditions after electroporation display reduced random integration frequency compared to that under normal (21%) oxygen conditions. These findings support the notion that Top2α protein and ROS are endogenous factors that can produce DNA damage leading to random integration of transfected DNA in human cells.

Endogenous Factors Causative of Spontaneous DNA Damage that Leads to Random Integration in Human Cells

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収録刊行物

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Endogenous Factors Causative of Spontaneous DNA Damage that Leads to Random Integration in Human Cells

説明

収録刊行物

関連プロジェクト

詳細情報 詳細情報について

書き出し

問題の指摘

詳細情報詳細情報について