A p.R369G POLG2 mutation associated with adPEO and multiple mtDNA deletions causes decreased affinity between polymerase 纬 subunits

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• 作者：Kate Craig^a ; ¹ ; Matthew J. Young^b ; ¹ ; Emma L. Blakely^a ; Matthew J. Longley^b ; Douglass M. Turnbull^a ; William C. Copeland^b ; Robert W. Taylor^a ; ^{robert.taylor@ncl.ac.uk}
• 关键词：Mitochondrial DNA polymerase ; POLG2 ; adPEO ; Multiple mtDNA deletions ; Recombinant enzyme ; Replication stalling
• 刊名：Mitochondrion
• 出版年：2012
• 期刊代码：39_15677249
• 类别：neu
• 出版时间：March, 2012
• 卷：12
• 期：2
• 页码：313-319
• 文件大小：679 K

摘要

Human mitochondrial DNA (mtDNA) polymerase 纬 (pol 纬) is the sole enzyme required to replicate and maintain the integrity of the mitochondrial genome. It comprises two subunits, a catalytic p140 subunit and a smaller p55 accessory subunit encoded by the POLG2 gene. We describe the molecular characterization of a potential dominant POLG2 mutation (p.R369G) in a patient with adPEO and multiple mtDNA deletions. Biochemical studies of the recombinant mutant p55 protein showed a reduced affinity to the pol 纬 p140 subunit, leading to impaired processivity of the holoenzyme complex but did not show sensitivity to N-ethylmalaimide (NEM) inhibition, inferring a novel disease mechanism.