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DOI | 10.1126/science.aao3172 |
Redox-sensitive alteration of replisome architecture safeguards genome integrity | |
Somyajit, Kumar1; Gupta, Rajat2; Sedlackova, Hana1; Neelsen, Kai John1; Ochs, Fena1; Rask, Maj-Britt1; Choudhary, Chunaram2; Lukas, Jiri1 | |
2017-11-10 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6364页码:797-802 |
文章类型 | Article |
语种 | 英语 |
国家 | Denmark |
英文摘要 | DNA replication requires coordination between replication fork progression and deoxynucleotide triphosphate (dNTP)-generating metabolic pathways. We find that perturbation of ribonucleotide reductase (RNR) in humans elevates reactive oxygen species (ROS) that are detected by peroxiredoxin 2 (PRDX2). In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS. Elevated ROS levels generated by RNR attenuation disrupt oligomerized PRDX2 to smaller subunits, whose dissociation from chromatin enforces the displacement of TIMELESS from the replisome. This process instantly slows replication fork progression, which mitigates pathological consequences of replication stress. Thus, redox signaling couples fluctuations of dNTP biogenesis with replisome activity to reduce stress during genome duplication. We propose that cancer cells exploit this pathway to increase their adaptability to adverse metabolic conditions. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000414847100047 |
WOS关键词 | REPLICATION STRESS ; DNA-REPLICATION ; HUMAN-CELLS ; PEROXIREDOXINS ; INSTABILITY ; STABILITY ; CANCER ; PHASE ; FORM |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197284 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Copenhagen, Prot Signaling Program, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark; 2.Univ Copenhagen, Prote Program, Novo Nordisk Fdn Ctr Prot Res, Fac Hlth & Med Sci, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark |
推荐引用方式 GB/T 7714 | Somyajit, Kumar,Gupta, Rajat,Sedlackova, Hana,et al. Redox-sensitive alteration of replisome architecture safeguards genome integrity[J]. SCIENCE,2017,358(6364):797-802. |
APA | Somyajit, Kumar.,Gupta, Rajat.,Sedlackova, Hana.,Neelsen, Kai John.,Ochs, Fena.,...&Lukas, Jiri.(2017).Redox-sensitive alteration of replisome architecture safeguards genome integrity.SCIENCE,358(6364),797-802. |
MLA | Somyajit, Kumar,et al."Redox-sensitive alteration of replisome architecture safeguards genome integrity".SCIENCE 358.6364(2017):797-802. |
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