[HTML][HTML] 6-Thioguanine damages mitochondrial DNA and causes mitochondrial dysfunction in human cells
I Daehn, R Brem, E Barkauskaite, P Karran - FEBS letters, 2011 - Elsevier
I Daehn, R Brem, E Barkauskaite, P Karran
FEBS letters, 2011•ElsevierThe anticancer and immunosuppressant thiopurines cause 6-thioguanine (6-TG) to
accumulate in nuclear DNA. We report that 6-TG is also readily incorporated into
mitochondrial DNA (mtDNA) where it is rapidly oxidized. The oxidized forms of mtDNA 6-TG
inhibit replication by DNA Pol-γ. Accumulation of oxidized 6-TG is associated with reduced
mtDNA transcription, a decline in mitochondrial protein levels, and loss of mitochondrial
function. Ultraviolet A radiation (UVA) also oxidizes mtDNA 6-TG. Cells without mtDNA are …
accumulate in nuclear DNA. We report that 6-TG is also readily incorporated into
mitochondrial DNA (mtDNA) where it is rapidly oxidized. The oxidized forms of mtDNA 6-TG
inhibit replication by DNA Pol-γ. Accumulation of oxidized 6-TG is associated with reduced
mtDNA transcription, a decline in mitochondrial protein levels, and loss of mitochondrial
function. Ultraviolet A radiation (UVA) also oxidizes mtDNA 6-TG. Cells without mtDNA are …
The anticancer and immunosuppressant thiopurines cause 6-thioguanine (6-TG) to accumulate in nuclear DNA. We report that 6-TG is also readily incorporated into mitochondrial DNA (mtDNA) where it is rapidly oxidized. The oxidized forms of mtDNA 6-TG inhibit replication by DNA Pol-γ. Accumulation of oxidized 6-TG is associated with reduced mtDNA transcription, a decline in mitochondrial protein levels, and loss of mitochondrial function. Ultraviolet A radiation (UVA) also oxidizes mtDNA 6-TG. Cells without mtDNA are less sensitive to killing by a combination of 6-TG and UVA than their mtDNA-containing counterparts, indicating that photochemical mtDNA 6-TG oxidation contributes to 6-TG-mediated UVA photosensitization.
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