耐辐射奇球菌毒素-抗毒素系统MazEF-dr在DNA损伤胁迫响应和调控中的作用机制

耐辐射奇球菌（DR）是一种能够忍受强烈电离辐射、化学诱变剂等DNA损伤剂压力的微生物，DNA损伤胁迫能引起基因表达水平变化并导致部分细胞凋亡等生理行为调控，DNA损伤胁迫响应和调控系统在其超强生存能力中起着重要作用。申请人前期研究发现了DR菌具有特殊RNA序列作用偏好性的毒素-抗毒素系统MazEF-dr，MazEF-dr突变能够解除菌体在DNA损伤胁迫下的细胞凋亡行为，表明MazEF-dr可能通过毒素MazF-dr识别和降解RNA功能参与了胁迫响应和行为调控。目前MazEF-dr的压力胁迫诱导和调控机制尚不清楚。本课题计划在前期研究基础上，研究并揭示MazEF-dr的DNA损伤胁迫诱导作用与条件、胞内作用靶点和调控等分子机制，阐明MazEF-dr在菌体压力胁迫响应和生理行为调控中的作用规律，旨在揭示耐辐射奇球菌应对DNA损伤胁迫的作用机制，为深入了解菌体极端环境生存机理提供基础和新的见解。

Deinococcus radiodurans (DR) is a bacterium which is known for its tolerance to extreme DNA damage stress including irradiation and chemical mutagens. DNA damage agents can induce changes of gene expression level and physiological behaviors including apoptosis of a fraction of cells. DNA damage stress-response and regulation system plays important roles in its exceptional survival under stresses. Our previous results identified the toxin-antitoxin system MazEF-dr with special sequence-preference on RNAs in D. radiodurans. Gene mutation of MazEF-dr relieved the apoptosis of D. radiodurans under DNA damage stress, indicating that the MazEF-dr was involved in the stress-response and physiological regulation through the recognition and cleavage on RNA by its toxin MazF-dr. The molecular mechanism of induction and regulation of MazEF-dr under DNA damage stress remains unclear. Based on our previous study, we plan to investigate the molecular mechanism including DNA damage stress-induction and conditions, cellular targets and regulation of MazEF-dr using biochemical and molecular biological methods. The objectives of this project are to elucidate the function mechanism of MazEF-dr in the DNA damage stress-response and physiological regulation and reveal the response mechanism of D. radiodurans to DNA damage stress. The results will provide fundament and novel insights to understanding the survival of D. radiodurans under extreme stresses.