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The accessory subunit of human DNA polymerase γ is required for mitochondrial DNA maintenance and is able to stabilize the catalytic subunit
Mitochondrion ( IF 3.9 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.mito.2020.05.008
Yura Do 1 , Shigeru Matsuda 1 , Teppei Inatomi 1 , Kazuto Nakada 2 , Takehiro Yasukawa 1 , Dongchon Kang 1
Affiliation  

Human DNA polymerase γ (POLG) is a mitochondria-specific replicative DNA polymerase consisting of a single catalytic subunit, POLGα, and a dimeric accessory subunit, POLGβ. To gain a deeper understanding of the role of POLGβ, we knocked out this protein in cultured human cybrid cells and established numerous knockout clones. POLGβ-knockout clones presented a clear phenotype of mitochondrial DNA loss, indicating that POLGβ is necessary for mitochondrial DNA replication. Moreover, POLGβ-knockout cells showed a severe decrease in POLGα levels and acute suppression of POLGβ expression efficiently down-regulated POLGα levels. These results suggest that, in addition to its role as the processivity factor of POLG, POLGβ acts as a POLGα stabilizer, an important role for POLGβ in mitochondrial DNA maintenance.

中文翻译:

人类 DNA 聚合酶 γ 的辅助亚基是线粒体 DNA 维持所必需的,并且能够稳定催化亚基

人类 DNA 聚合酶 γ (POLG) 是一种线粒体特异性复制 DNA 聚合酶,由单个催化亚基 POLGα 和二聚辅助亚基 POLGβ 组成。为了更深入地了解 POLGβ 的作用,我们在培养的人类 cybrid 细胞中敲除这种蛋白质并建立了许多敲除克隆。POLGβ 敲除克隆表现出明显的线粒体 DNA 丢失表型,表明 POLGβ 是线粒体 DNA 复制所必需的。此外,敲除 POLGβ 的细胞显示出 POLGα 水平的严重下降和 POLGβ 表达的急性抑制有效下调了 POLGα 水平。这些结果表明,除了作为 POLG 的持续合成因子的作用外,POLGβ 还充当 POLGα 稳定剂,这是 POLGβ 在线粒体 DNA 维持中的重要作用。
更新日期:2020-07-01
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