DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance.
DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance.
复制标题
作者：
DNA损伤反应的特征在于其细胞自主检查点功能，导致细胞周期停滞、衰老和凋亡。相比之下，对组织特异性基因组不稳定性的系统反应仍然知之甚少。在成人C.蠕虫生殖细胞经历有丝分裂和减数分裂，而体细胞组织完全是有丝分裂后的。因此，DNA损伤检查点在生殖细胞中特异性地起作用，而在成体C.秀丽隐杆线虫对辐射有很强的抵抗力一些DNA修复系统，如全球基因组核苷酸切除修复（GG-NER），专门消除生殖细胞中的病变。在这里，我们研究了生殖细胞基因组的不稳定性如何影响体细胞组织在C。优雅我们表明，外源性和内源性DNA损伤的生殖细胞引起的耐热性和氧化应激的提高。体细胞应激抗性由生殖细胞中的ERK MAP激酶MPK-1介导，其触发与先天免疫相关的推定分泌肽的诱导。先天免疫应答导致体组织中泛素-蛋白酶体系统（UPS）的激活，其赋予增强的蛋白质稳态和系统性应激抗性。我们建议，提高系统性应激抵抗力促进体细胞组织的耐力，以允许延迟后代生产时，生殖细胞基因组受损。
DNA damage responses have been well characterized in their cell-autonomous checkpoint functions leading to cell cycle arrest, senescence, and apoptosis . In contrast, systemic responses to tissue-specific genome instability remain poorly understood. In adult C. elegans worms germ cells undergo mitotic and meiotic cell divisions while somatic tissues are entirely postmitotic. Consequently, DNA damage checkpoints function specifically in the germline , whereas somatic tissues in adult C. elegans are highly radio-resistant . Some DNA repair systems such as global-genome nucleotide excision repair (GG-NER) remove lesions specifically in germ cells . Here we investigated how genome instability in germ cells affects somatic tissues in C. elegans. We show that exogenous and endogenous DNA damage in germ cells evokes elevated resistance to heat and oxidative stress. The somatic stress resistance is mediated by the ERK MAP kinase MPK-1 in germ cells that triggers the induction of putative secreted peptides associated with innate immunity. The innate immune response leads to activation of the ubiquitin-proteasome system (UPS) in somatic tissues, which confers enhanced proteostasis and systemic stress resistance. We propose that elevated systemic stress resistance promotes endurance of somatic tissues to allow delay of progeny production when germ cells are genomically compromised.
登录
查看更多内容
影响因子：
9.2
作者：
Nicholas, HR;Hodgkin, J
通讯作者：
Hodgkin, J
影响因子：
11.8
作者：
Colaiácovo, MP;MacQueen, AJ;Villeneuve, AM
通讯作者：
Villeneuve, AM
影响因子：
16
作者：
Gartner, A;Milstein, S;Hengartner, MO
通讯作者：
Hengartner, MO
影响因子：
7
作者：
O'Rourke, Delia;Baban, Dilair;Hodgkin, Jonathan
通讯作者：
Hodgkin, Jonathan
Wolf Psort：蛋白质定位预测因子。
影响因子：
14.9
作者：
Horton, Paul;Park, Keun-Joon;Obayashi, Takeshi;Fujita, Naoya;Harada, Hajime;Adams-Collier, C J;Nakai, Kenta
通讯作者：
Nakai, Kenta