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本文引用的文献

1
Human DNA2 is a mitochondrial nuclease/helicase for efficient processing of DNA replication and repair intermediates.人类DNA2是一种线粒体核酸酶/解旋酶，用于高效处理DNA复制和修复中间体。
Mol Cell. 2008 Nov 7;32(3):325-36. doi: 10.1016/j.molcel.2008.09.024.
2
Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling.与常染色体显性进行性眼外肌麻痹相关的Twinkle突变导致解旋酶功能受损和体内线粒体DNA复制停滞。
Hum Mol Genet. 2009 Jan 15;18(2):328-40. doi: 10.1093/hmg/ddn359. Epub 2008 Oct 29.
3
Identification of the Xenopus DNA2 protein as a major nuclease for the 5'->3' strand-specific processing of DNA ends.非洲爪蟾DNA2蛋白被鉴定为DNA末端5'->3'链特异性加工的主要核酸酶。
Nucleic Acids Res. 2008 Nov;36(19):6091-100. doi: 10.1093/nar/gkn616. Epub 2008 Sep 27.
4
Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends.Sgs1解旋酶以及两种核酸酶Dna2和Exo1切除DNA双链断裂末端。
Cell. 2008 Sep 19;134(6):981-94. doi: 10.1016/j.cell.2008.08.037.
5
Infantile-onset spinocerebellar ataxia and mitochondrial recessive ataxia syndrome are associated with neuronal complex I defect and mtDNA depletion.婴儿期起病的脊髓小脑共济失调和线粒体隐性共济失调综合征与神经元复合体I缺陷和线粒体DNA耗竭有关。
Hum Mol Genet. 2008 Dec 1;17(23):3822-35. doi: 10.1093/hmg/ddn280. Epub 2008 Sep 5.
6
The Schizosaccharomyces pombe Pfh1p DNA helicase is essential for the maintenance of nuclear and mitochondrial DNA.粟酒裂殖酵母Pfh1p DNA解旋酶对于维持核DNA和线粒体DNA至关重要。
Mol Cell Biol. 2008 Nov;28(21):6594-608. doi: 10.1128/MCB.00191-08. Epub 2008 Aug 25.
7
Removal of oxidative DNA damage via FEN1-dependent long-patch base excision repair in human cell mitochondria.通过人细胞线粒体中FEN1依赖的长片段碱基切除修复去除氧化性DNA损伤。
Mol Cell Biol. 2008 Aug;28(16):4975-87. doi: 10.1128/MCB.00457-08. Epub 2008 Jun 9.
8
Mitochondrial DNA, base excision repair and neurodegeneration.线粒体DNA、碱基切除修复与神经退行性变
DNA Repair (Amst). 2008 Jul 1;7(7):1098-109. doi: 10.1016/j.dnarep.2008.03.011. Epub 2008 May 16.
9
Flap endonuclease 1 contributes to telomere stability.瓣内切核酸酶1有助于端粒稳定性。
Curr Biol. 2008 Apr 8;18(7):496-500. doi: 10.1016/j.cub.2008.02.071.
10
Mitochondrial base excision repair of uracil and AP sites takes place by single-nucleotide insertion and long-patch DNA synthesis.线粒体对尿嘧啶和脱嘌呤嘧啶位点的碱基切除修复通过单核苷酸插入和长片段DNA合成进行。
DNA Repair (Amst). 2008 Apr 2;7(4):605-16. doi: 10.1016/j.dnarep.2008.01.002. Epub 2008 Mar 4.

人类Dna2是一种细胞核和线粒体DNA维持蛋白。

Human Dna2 is a nuclear and mitochondrial DNA maintenance protein.

作者信息

Duxin Julien P, Dao Benjamin, Martinsson Peter, Rajala Nina, Guittat Lionel, Campbell Judith L, Spelbrink Johannes N, Stewart Sheila A

机构信息

Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

出版信息

Mol Cell Biol. 2009 Aug;29(15):4274-82. doi: 10.1128/MCB.01834-08. Epub 2009 Jun 1.

DOI:10.1128/MCB.01834-08
PMID:19487465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2715806/
Abstract

Dna2 is a highly conserved helicase/nuclease that in yeast participates in Okazaki fragment processing, DNA repair, and telomere maintenance. Here, we investigated the biological function of human Dna2 (hDna2). Immunofluorescence and biochemical fractionation studies demonstrated that hDna2 was present in both the nucleus and the mitochondria. Analysis of mitochondrial hDna2 revealed that it colocalized with a subfraction of DNA-containing mitochondrial nucleoids in unperturbed cells. Upon the expression of disease-associated mutant forms of the mitochondrial Twinkle helicase which induce DNA replication pausing/stalling, hDna2 accumulated within nucleoids. RNA interference-mediated depletion of hDna2 led to a modest decrease in mitochondrial DNA replication intermediates and inefficient repair of damaged mitochondrial DNA. Importantly, hDna2 depletion also resulted in the appearance of aneuploid cells and the formation of internuclear chromatin bridges, indicating that nuclear hDna2 plays a role in genomic DNA stability. Together, our data indicate that hDna2 is similar to its yeast counterpart and is a new addition to the growing list of proteins that participate in both nuclear and mitochondrial DNA maintenance.

摘要

Dna2是一种高度保守的解旋酶/核酸酶，在酵母中参与冈崎片段加工、DNA修复和端粒维持。在此，我们研究了人类Dna2（hDna2）的生物学功能。免疫荧光和生化分级分离研究表明，hDna2存在于细胞核和线粒体中。对线粒体hDna2的分析显示，在未受干扰的细胞中，它与含DNA的线粒体类核的一个亚组分共定位。在线粒体Twinkle解旋酶的疾病相关突变形式表达时，会诱导DNA复制暂停/停滞，hDna2会在类核中积累。RNA干扰介导的hDna2缺失导致线粒体DNA复制中间体适度减少，受损线粒体DNA的修复效率低下。重要的是，hDna2缺失还导致非整倍体细胞的出现和核间染色质桥的形成，表明核hDna2在基因组DNA稳定性中发挥作用。总之，我们的数据表明，hDna2与其酵母对应物相似，是参与核和线粒体DNA维持的蛋白质不断增加的列表中的新成员。