Nature：免疫细胞死亡体验促进功能发育

　　

生物通报道，华盛顿大学医学院病理和免疫学研究室、国立卫生研究所分支机构环境卫生科学研究中心环境影响与癌症研究小组、费城大学医学院儿童肿瘤医院、费城Abramson家族癌症研究所的研究者对淋巴细胞发育过程进行研究，结果发现，祖代细胞在发育过程中出现DNA双链断裂的现象，这一现象不仅不会影响淋巴细胞的发育，还能激活基因重组促进淋巴细胞发育成多功能的细胞。相关的研究成果发表在10月12号的Nature上。

 

DNA双链在某些遗传毒性环境、某些生理过程中细胞核酸内切酶介导下发生断裂。一般情况下，DNA遇上遗传毒性环境发生断裂的生物学意义是激活某些原始的细胞复制检测系统，确保细胞内DNA的完整性，一旦出现错误可诱导异常的细胞死亡。

 

研究者发现，所有的淋巴细胞在发育的过程中都发生过DNA双链断裂的现象，这一现象都发生在抗原受体基因装配的过程，抗原受体基因装配是淋巴细胞发育的一个关键的过程。

 

研究小组以小鼠的淋巴细胞为研究模型，揭示了DNA双链断裂现象可激活淋巴细胞大量的转录程序。研究者发现，与往常所遇到的遗传毒性的DNA双链断裂事件不同的是，免疫细胞的DNA双链断裂常诱发多种转录程序启动，影响多种对生理现象有调节作用的基因。有些转录的基因在遗传毒性环境下也发生相同的转录。

 

研究者最终发现，生理上的DNA双链断裂会促进细胞发育成为特殊功能的细胞且不影响基因组的完整性，而遗传毒性导致的DNA双链断裂往往只会破坏基因组的完整性，破坏各种生理学过程。

 

原文摘要：DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes

 

【Abstract】

DNA double-strand breaks are generated by genotoxic agents and by cellular endonucleases as intermediates of several important physiological processes. The cellular response to genotoxic DNA breaks includes the activation of transcriptional programs known primarily to regulate cell-cycle checkpoints and cell survival. DNA double-strand breaks are generated in all developing lymphocytes during the assembly of antigen receptor genes, a process that is essential for normal lymphocyte development. Here we show that in murine lymphocytes these physiological DNA breaks activate a broad transcriptional program. This program transcends the canonical DNA double-strand break response and includes many genes that regulate diverse cellular processes important for lymphocyte development. Moreover, the expression of several of these genes is regulated similarly in response to genotoxic DNA damage. Thus, physiological DNA double-strand breaks provide cues that can regulate cell-type-specific processes not directly involved in maintaining the integrity of the genome, and genotoxic DNA breaks could disrupt normal cellular functions by corrupting these processes.