Maintenance of Flap Endonucleases for Long-Patch Base Excision DNA Repair in Mouse Muscle and Neuronal Cells Differentiated In Vitro.
Maintenance of Flap Endonucleases for Long-Patch Base Excision DNA Repair in Mouse Muscle and Neuronal Cells Differentiated In Vitro.
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DOI：
10.3390/ijms241612715
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发表时间：
2023-08-12
影响因子：
5.6
通讯作者：
Demple, Bruce
中科院分区：
文献类型：
--
作者：
Caston, Rachel A.;Fortini, Paola;Chen, Kevin;Bauer, Jack;Dogliotti, Eugenia;Yin, Y. Whitney;Demple, Bruce
关键词：
细胞分化后，核DNA不再复制，许多相关蛋白质相应下调。这些包括结构特异性核酸内切酶Fen1和DNA2，它们与修复线粒体DNA（mtDNA）有关。在线粒体中发现了另外两种这样的核酸内切酶，命名为MGME 1和ExoG。这类核酸酶是所谓的“长斑”（多核苷酸）碱基切除DNA修复（BER）所必需的，这是处理某些氧化损伤所必需的，这引发了分化如何影响线粒体中这些酶的可用性和使用的问题。在这项研究中，我们证明，Fen1和DNA2确实强烈下调后分化的神经元前体（导管a分化细胞）或小鼠肌管，而MGME 1和ExoG的表达水平显示最小的变化。这些细胞的线粒体提取物中的总瓣切除活性在分化后适度降低，MGME 1作为主要的瓣核酸内切酶，ExoG发挥较小的作用。出乎意料的是，这两种分化的细胞类型似乎在mtDNA中积累的氧化或烷基化损伤比它们的增殖祖细胞少。最后，线粒体DNA修复的总体速率在增殖和分化细胞之间没有显著差异。综上所述，这些结果表明，神经元细胞在分化后维持mtDNA修复，显然依赖于长补丁BER的ESTA特异性酶。
After cellular differentiation, nuclear DNA is no longer replicated, and many of the associated proteins are downregulated accordingly. These include the structure-specific endonucleases Fen1 and DNA2, which are implicated in repairing mitochondrial DNA (mtDNA). Two more such endonucleases, named MGME1 and ExoG, have been discovered in mitochondria. This category of nuclease is required for so-called “long-patch” (multinucleotide) base excision DNA repair (BER), which is necessary to process certain oxidative lesions, prompting the question of how differentiation affects the availability and use of these enzymes in mitochondria. In this study, we demonstrate that Fen1 and DNA2 are indeed strongly downregulated after differentiation of neuronal precursors (Cath.a-differentiated cells) or mouse myotubes, while the expression levels of MGME1 and ExoG showed minimal changes. The total flap excision activity in mitochondrial extracts of these cells was moderately decreased upon differentiation, with MGME1 as the predominant flap endonuclease and ExoG playing a lesser role. Unexpectedly, both differentiated cell types appeared to accumulate less oxidative or alkylation damage in mtDNA than did their proliferating progenitors. Finally, the overall rate of mtDNA repair was not significantly different between proliferating and differentiated cells. Taken together, these results indicate that neuronal cells maintain mtDNA repair upon differentiation, evidently relying on mitochondria-specific enzymes for long-patch BER.
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DOI：
10.3109/19401736.2014.905829
发表时间：
2016
期刊：
Mitochondrial DNA. Part A, DNA mapping, sequencing, and analysis
影响因子：
--
作者：
Shokolenko IN;Wilson GL;Alexeyev MF
通讯作者：
Alexeyev MF
影响因子：
3.3
作者：
Nouspikel, T.
通讯作者：
Nouspikel, T.
影响因子：
16.6
作者：
Matic S;Jiang M;Nicholls TJ;Uhler JP;Dirksen-Schwanenland C;Polosa PL;Simard ML;Li X;Atanassov I;Rackham O;Filipovska A;Stewart JB;Falkenberg M;Larsson NG;Milenkovic D
通讯作者：
Milenkovic D
DOI：
10.1007/978-1-62703-739-6_31
发表时间：
2014
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Furda, Amy;Santos, Janine H;Meyer, Joel N;Van Houten, Bennett
通讯作者：
Van Houten, Bennett
影响因子：
4.8
作者：
Kao, KI;Henricksen, LA;Bambara, RA
通讯作者：
Bambara, RA