Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada.
J Mol Histol. 2013 Aug;44(4):481-94. doi: 10.1007/s10735-013-9496-5. Epub 2013 Mar 28.
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that processes blocked 3' ends of DNA breaks. Functional loss of Tdp1 causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Based on the prominent cytoplasmic expression of Tdp1 in the neurons presumably affected in SCAN1, we hypothesized that Tdp1 participates in the repair of mitochondrial DNA. As a step toward testing this hypothesis, we profiled Tdp1 expression in different human tissues by immunohistochemistry and immunofluorescence respectively and determined whether Tdp1 was expressed in the cytoplasm of tissues other than the neurons. We found that Tdp1 was ubiquitously expressed and present in the cytoplasm of many cell types. Within human skeletal muscle and multiple mouse tissues, Tdp1 partially colocalized with the mitochondria. In cultured human dermal fibroblasts, Tdp1 redistributed to the cytoplasm and partially colocalized with mitochondria following oxidative stress. These studies suggest that one role of cytoplasmic Tdp1 is the repair of mitochondrial DNA lesions arising from oxidative stress.
酪氨酰-DNA 磷酸二酯酶 1（Tdp1）是一种 DNA 修复酶，可处理 DNA 断裂的受阻 3' 末端。Tdp1 的功能丧失会导致脊髓小脑共济失调伴轴索性神经病 1 型（SCAN1）。基于 Tdp1 在推测受 SCAN1 影响的神经元中明显的细胞质表达，我们假设 Tdp1 参与了线粒体 DNA 的修复。为了验证这一假设，我们分别通过免疫组织化学和免疫荧光法对不同的人组织中的 Tdp1 表达进行了分析，并确定 Tdp1 是否表达在除神经元以外的组织的细胞质中。我们发现 Tdp1 在许多细胞类型中广泛表达并存在于细胞质中。在人类骨骼肌和多种小鼠组织中，Tdp1 与线粒体部分共定位。在培养的人真皮成纤维细胞中，Tdp1 在氧化应激后重新分布到细胞质中，并与线粒体部分共定位。这些研究表明，细胞质 Tdp1 的一个作用是修复氧化应激引起的线粒体 DNA 损伤。
