GSTDTAP  > 地球科学
DOI10.1126/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
ISSN0036-8075
EISSN1095-9203
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
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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
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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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