Tight control of genomic phosphorothioate modification by the ATP-modulated autoregulation and reusability of DndB

被引：12

作者：

Xia, Sisi ^{[1
,2
]}

Chen, Jun ^{[3
]}

Liu, Liqiong ^{[1
]}

Wei, Yue ^{[1
]}

Deng, Zixin ^{[1
]}

Wang, Lianrong ^{[1
]}

Chen, Shi ^{[1
,2
]}

机构：

[1] Wuhan Univ, Zhongnan Hosp, Key Lab Combinatorial Biosynth & Drug Discovery, Minist Educ,Sch Pharmaceut Sci, Wuhan 430071, Hubei, Peoples R China

[2] Hubei Univ Med, Taihe Hosp, Shiyan 442000, Peoples R China

[3] Jinan Univ, Dept Biotechnol, Coll Life Sci & Technol, Guangzhou 510632, Guangdong, Peoples R China

来源：

MOLECULAR MICROBIOLOGY | 2019年 / 111卷 / 04期

基金：

中国国家自然科学基金;

关键词：

ESCHERICHIA-COLI; DNA PHOSPHOROTHIOATION; MODIFICATION SYSTEM; RESTRICTION SYSTEM; S-MODIFICATION; PROTEIN; METHYLTRANSFERASE; EXPRESSION; EPIGENETICS; INDUCTION;

D O I：

10.1111/mmi.14186

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA phosphorothioate (PT) modification was recently identified to occur naturally in diverse bacteria and to be governed by DndABCDE proteins. The nuclease resistance as well as the redox and nucleophilic properties of PT sulfur make PT modification a versatile player in restriction-modification (R-M) defense, epigenetic regulation, environmental fitness and the maintenance of cellular redox homeostasis. In this study, we discovered that tight control of PT levels is mediated by the ATPase activity of DndB. The ATP-binding activity of DndB stimulates the dissociation of the DndB-DNA complex, allowing transcriptional initiation, whereas its ATP hydrolysis activity promotes the conversion of DndB-ATP to free DndB that is capable of rebinding to promoter DNA for transcriptional inhibition. Since sulfur incorporation is an ATP-consuming process, these activities provide an economical way to fine-tune PT modification in an ATP-sensing manner. To our knowledge, this ATP-mediated regulation is a rare example among DNA epigenetic modification systems; the features of autoregulation and the repeated usage of DndB allow the dedicated regulation of PT levels in response to cellular ATP concentrations, providing insight into PT function and its role in physiology.

引用

页码：938 / 950

页数：13