Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells

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• 作者：Jaakko L.O. Pohjoism&#xe4 ; ki^a ; ^{Jaakko.Pohjoismaeki@mpi-bn.mpg.de"" rel=""nofollow} ; Steffi Goffart^b ; Johannes N. Spelbrink^b ; ^c
• 关键词：mtDNA replication ; Replication stall ; Recombination ; Repair ; Twinkle
• 刊名：Mitochondrion
• 出版年：2011
• 出版时间：July 2011
• 年：2011
• 卷：11
• 期：4
• 页码：630-634
• 全文大小：1142 K

文摘

Pathological mitochondrial DNA (mtDNA) rearrangements have been proposed to result from repair of double-strand breaks caused by blockage of mitochondrial DNA (mtDNA) replication. As mtDNA deletions are seen only in post-mitotic tissues, it has been suggested that they are selected out in actively dividing cells. By electron microscopy we observed rearranged mtDNA molecules in cultured human cells expressing a catalytically impaired helicase. As these molecules were undetectable by PCR, we propose that deleted mtDNA molecules in cultured cells are fragile and sensitive to heating. Further consequences of mtDNA replication stalling are discussed.