SCI
26February
Autophagiccelldeathrestrictschromosomalinstabilityduringreplicativecrisis
NassourJ,RadfordR,CorreiaA,etal.Autophagiccelldeathrestrictschromosomalinstabilityduringreplicativecrisis.Nature;:-63.
CorrespondenceandrequestsformaterialsshouldbeaddressedtoJ.K.InstituteofHumanGenetics,UniversityofHeidelberg,Heidelberg,Germany.*e-mail:karlseder
salk.eduReplicativecrisisisasenescence-independentprocessthatactsasafinalbarrieragainstoncogenictransformationbyeliminatingprecancerouscellswithdisruptedcellcyclecheckpoints.Itfunctionsasapotenttumoursuppressorandculminatesinextensivecelldeath.Cellsrarelyevadeeliminationandevolvetowardsmalignancy,butthemechanismsthatunderliecelldeathincrisisarenotwellunderstood.
“复制危机”是一个与衰老无关的过程，它通过破坏细胞周期检查点来消除癌前细胞，从而成为阻止致癌转化的最后一道屏障。它可以发挥有效的肿瘤抑制功能，并最终致使广泛的细胞死亡。细胞很少能豁免死亡向恶性发展，但“危机”中细胞死亡的机制尚不清楚。
Hereweshowthatmacroautophagyhasadominantroleinthedeathoffibroblastsandepithelialcellsduringcrisis.Activationofautophagyiscriticalforcelldeath,asitssuppressionpromotedbypassofcrisis,continuedproliferationandaccumulationofgenomeinstability.Telomeredysfunctionspecificallytriggersautophagy,implicatingatelomere-drivenautophagypathwaythatisnotinducedbyintrachromosomalbreaks.TelomericDNAdamagegeneratescytosolicDNAspecieswithfragilenuclearenvelopesthatundergospontaneousdisruption.
在这里，我们展示了大自噬对成纤维细胞和上皮细胞在“危机”中死亡的主要作用。自噬的激活对细胞死亡至关重要，因为对其的抑制可以促进了“危机”的绕过，增殖继续和基因组不稳定的积累。端粒功能障碍特异性触发自噬，提示端粒驱动的自噬通路不是由染色体内断裂诱导的。端粒DNA损伤产生细胞质DNA的物种，其核膜脆弱，可发生自发破坏。
ThecytosolicchromatinfragmentsactivatethecGAS–STING(cyclicGMP-AMPsynthase–stimulatorofinterferongenes)pathwayandengagetheautophagymachinery.Ourdatasuggestthatautophagyisanintegral白癜风怎么引起的白癜风可以治得好吗
