酵母拓扑异构酶 I 对 DNA 中核糖核苷酸的诱变处理。
Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.
机构信息
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Science. 2011 Jun 24;332(6037):1561-4. doi: 10.1126/science.1205016.
Abstract
The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism. RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its absence in budding yeast has been associated with the accumulation of deletions within short tandem repeats. Here, we demonstrate that rNMP-associated deletion formation requires the activity of Top1, a topoisomerase that relaxes supercoils by reversibly nicking duplex DNA. The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease.
摘要
核糖核酸酶 (RNase) H 类酶可降解 RNA:DNA 杂合体中的 RNA 成分，在核酸代谢中具有重要作用。RNase H2 专门从双链 DNA 中去除单个核苷酸[核苷单磷酸 (rNMP)]，芽殖酵母中该酶的缺失与短串联重复序列内的缺失积累有关。在这里，我们证明 rNMP 相关的缺失形成需要 Top1 的活性，Top1 是一种拓扑异构酶，通过可逆地切割双链 DNA 来松弛超螺旋。已报道的研究将 Top1 的作用扩展到包括将 rNMP 在基因组 DNA 中加工成不可逆的单链断裂，这种活性可能具有不同的诱变后果，并且可能与人类疾病相关。
相似文献
1
Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I.酵母拓扑异构酶 I 对 DNA 中核糖核苷酸的诱变处理。
Science. 2011 Jun 24;332(6037):1561-4. doi: 10.1126/science.1205016.
2
Two distinct mechanisms of Topoisomerase 1-dependent mutagenesis in yeast.酵母中拓扑异构酶 1 依赖性突变的两种不同机制。
DNA Repair (Amst). 2013 Mar 1;12(3):205-11. doi: 10.1016/j.dnarep.2012.12.004. Epub 2013 Jan 8.
3
Molecular biology. A new twist for topoisomerase.分子生物学。拓扑异构酶的新变化。
Science. 2011 Jun 24;332(6037):1510-1. doi: 10.1126/science.1208450.
4
High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase.高浓度未修复的基因组核糖核苷酸导致拓扑异构酶 1 介导的核糖核苷酸还原酶缺乏时严重的生长缺陷。
Nucleic Acids Res. 2020 May 7;48(8):4274-4297. doi: 10.1093/nar/gkaa103.
5
Topoisomerase 1-mediated removal of ribonucleotides from nascent leading-strand DNA.拓扑异构酶 1 介导的新生前导链 DNA 中核苷酸的去除。
Mol Cell. 2013 Mar 7;49(5):1010-5. doi: 10.1016/j.molcel.2012.12.021. Epub 2013 Jan 31.
6
Studying Topoisomerase 1-Mediated Damage at Genomic Ribonucleotides.研究基因组核糖核苷酸上拓扑异构酶1介导的损伤。
Methods Mol Biol. 2018;1703:241-257. doi: 10.1007/978-1-4939-7459-7_17.
7
RNases H1 and H2: guardians of the stability of the nuclear genome when supply of dNTPs is limiting for DNA synthesis.RNase H1 和 H2：当 dNTP 供应限制 DNA 合成时，核基因组稳定性的守护者。
Curr Genet. 2020 Dec;66(6):1073-1084. doi: 10.1007/s00294-020-01086-8. Epub 2020 Sep 4.
8
Topoisomerase I alone is sufficient to produce short DNA deletions and can also reverse nicks at ribonucleotide sites.单独的拓扑异构酶I足以产生短的DNA缺失，并且还能修复核糖核苷酸位点处的切口。
J Biol Chem. 2015 May 29;290(22):14068-76. doi: 10.1074/jbc.M115.653345. Epub 2015 Apr 17.
9
Topoisomerase 1-dependent deletions initiated by incision at ribonucleotides are biased to the non-transcribed strand of a highly activated reporter.由核糖核苷酸切口引发的拓扑异构酶1依赖性缺失偏向于高度活化报告基因的非转录链。
Nucleic Acids Res. 2015 Oct 30;43(19):9306-13. doi: 10.1093/nar/gkv824. Epub 2015 Aug 13.
10
The role of topoisomerase I in suppressing genome instability associated with a highly transcribed guanine-rich sequence is not restricted to preventing RNA:DNA hybrid accumulation.拓扑异构酶I在抑制与高转录富含鸟嘌呤序列相关的基因组不稳定中的作用并不局限于防止RNA:DNA杂交积累。
Nucleic Acids Res. 2016 Jan 29;44(2):718-29. doi: 10.1093/nar/gkv1152. Epub 2015 Nov 2.
引用本文的文献
1
Epigenetic control of topoisomerase 1 activity presents a cancer vulnerability.拓扑异构酶1活性的表观遗传调控呈现出一种癌症易感性。
Nat Commun. 2025 Aug 12;16(1):7458. doi: 10.1038/s41467-025-62598-w.
2
Human reveal DNA-embedded ribonucleotides as a new type of epigenetic mark.人类揭示了嵌入DNA的核糖核苷酸作为一种新型表观遗传标记。
bioRxiv. 2025 Jun 30:2025.06.27.661996. doi: 10.1101/2025.06.27.661996.
3
The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.人类线粒体拓扑异构酶1的低核糖核酸酶活性和对核糖核苷酸的不偏好性可防止核糖核苷酸依赖性缺失。
Nucleic Acids Res. 2025 Jun 6;53(11). doi: 10.1093/nar/gkaf475.
4
Untargeted Mutation Triggered by Ribonucleoside Embedded in DNA.嵌入DNA中的核糖核苷引发的非靶向突变
Int J Mol Sci. 2024 Dec 22;25(24):13708. doi: 10.3390/ijms252413708.
5
Genome Instability Induced by Topoisomerase Misfunction.拓扑异构酶功能障碍导致的基因组不稳定性。
Int J Mol Sci. 2024 Sep 24;25(19):10247. doi: 10.3390/ijms251910247.
6
Second generation lethality in RNAseH2a knockout zebrafish.RNAseH2a 敲除斑马鱼的第二代致死率。
Nucleic Acids Res. 2024 Oct 14;52(18):11014-11028. doi: 10.1093/nar/gkae725.
7
From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.从顶部开始：拓扑异构酶 DNA 蛋白交联的形成、识别和解决。
DNA Repair (Amst). 2024 Oct;142:103751. doi: 10.1016/j.dnarep.2024.103751. Epub 2024 Aug 16.
8
Human DNA topoisomerase I poisoning causes R loop-mediated genome instability attenuated by transcription factor IIS.人类 DNA 拓扑异构酶 I 中毒导致转录因子 IIS 减弱的 R 环介导的基因组不稳定性。
Sci Adv. 2024 May 24;10(21):eadm8196. doi: 10.1126/sciadv.adm8196.
9
Detection of ribonucleotides embedded in DNA by Nanopore sequencing.通过纳米孔测序检测嵌入DNA中的核糖核苷酸。
Commun Biol. 2024 Apr 23;7(1):491. doi: 10.1038/s42003-024-06077-w.
10
Deletions initiated by the vaccinia virus TopIB protein in yeast.痘苗病毒 TopIB 蛋白在酵母中引发的缺失。
DNA Repair (Amst). 2024 May;137:103664. doi: 10.1016/j.dnarep.2024.103664. Epub 2024 Mar 6.
本文引用的文献
1
Mismatch repair-independent tandem repeat sequence instability resulting from ribonucleotide incorporation by DNA polymerase ε.DNA 聚合酶 ε 通过核苷酸掺入导致的错配修复非依赖性串联重复序列不稳定。
DNA Repair (Amst). 2011 May 5;10(5):476-82. doi: 10.1016/j.dnarep.2011.02.001. Epub 2011 Mar 16.
2
Topoisomerase 1 provokes the formation of short deletions in repeated sequences upon high transcription in Saccharomyces cerevisiae.拓扑异构酶 1 在酿酒酵母高转录时引发重复序列形成短缺失。
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):692-7. doi: 10.1073/pnas.1012582108. Epub 2010 Dec 21.
3
The importance of being DNA.身为DNA的重要性。
Cell Cycle. 2010 Nov 15;9(22):4422-4. doi: 10.4161/cc.9.22.14052.
4
DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.DNA拓扑异构酶及其被抗癌和抗菌药物抑制的情况。
Chem Biol. 2010 May 28;17(5):421-33. doi: 10.1016/j.chembiol.2010.04.012.
5
DNA cleavage assay for the identification of topoisomerase I inhibitors.用于鉴定拓扑异构酶I抑制剂的DNA切割试验
Nat Protoc. 2008;3(11):1736-50. doi: 10.1038/nprot.2008.174.
6
Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.酵母中的转录相关诱变与基因表达水平直接成正比，并受DNA复制方向的影响。
DNA Repair (Amst). 2007 Sep 1;6(9):1285-96. doi: 10.1016/j.dnarep.2007.02.023. Epub 2007 Mar 29.
7
Repair of topoisomerase I-mediated DNA damage.拓扑异构酶I介导的DNA损伤修复。
Prog Nucleic Acid Res Mol Biol. 2006;81:179-229. doi: 10.1016/S0079-6603(06)81005-6.
8
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.编码核糖核酸酶H2亚基的基因突变会导致Aicardi-Goutières综合征，并类似先天性病毒性脑感染。
Nat Genet. 2006 Aug;38(8):910-6. doi: 10.1038/ng1842. Epub 2006 Jul 16.
9
RNase H2 of Saccharomyces cerevisiae is a complex of three proteins.酿酒酵母的核糖核酸酶H2是一种由三种蛋白质组成的复合体。
Nucleic Acids Res. 2004 Jan 20;32(2):407-14. doi: 10.1093/nar/gkh209. Print 2004.
10
Correlation of somatic hypermutation specificity and A-T base pair substitution errors by DNA polymerase eta during copying of a mouse immunoglobulin kappa light chain transgene.在小鼠免疫球蛋白κ轻链转基因复制过程中，DNA聚合酶η的体细胞超突变特异性与A-T碱基对替换错误的相关性。
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9954-9. doi: 10.1073/pnas.152126799. Epub 2002 Jul 15.
Zotero 插件