DNA骨架磷硫酰化修饰的研究进展

doi:10.6023/A12121120

化学学报 ›› 2013, Vol. 71 ›› Issue (04): 501-507.DOI: 10.6023/A12121120 上一篇下一篇

综述

DNA骨架磷硫酰化修饰的研究进展

胡中培^a,b, 王呈坤^b, 蓝文贤^b, 李芳^a, 曹春阳^b

a 华中师范大学化学学院武汉 430079;
b 中国科学院上海有机化学研究所生命有机化学国家重点实验室上海 200032

投稿日期:2012-12-31 发布日期:2013-02-06
通讯作者: 李芳, 曹春阳 E-mail:f.li@mail.ccnu.edu.cn; ccao@mail.sioc.ac.cn
基金资助:
项目受国家科技部重大研究计划(Nos. 2009CB918600, 2011CB966300)和国家自然科学基金(Nos. 20905074, 21272261)资助.

Recent Advances in DNA Phosphorothioation Modification Studies

Hu Zhongpei^a,b, Wang Chengkun^b, Lan Wenxian^b, Li Fang^a, Cao Chunyang^b

a College of Chemistry, Central China University, Wuhan 430079;
b State Key Lab of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2012-12-31 Published:2013-02-06
Supported by:
Project supported by the National Basic Research Program of China (Nos. 2009CB918600, 2011CB966300) and the National Natural Science Foundation of China (Nos. 20905074, 21272261).

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摘要/Abstract

DNA骨架磷硫酰化修饰是指在天然DNA骨架上发现的P—O键被P—S键替换的化学修饰, 属于首例生理修饰, 具有磷硫修饰的DNA在Tris缓冲体系中电泳时具有DNA降解表型. 研究发现DNA骨架磷硫修饰属于复制后修饰, 具有如下三个特征: R_p型立体修饰, 序列专一性、分布广泛性. 这种修饰由五个基因组成的dnd基因簇(dndA-E)编码的蛋白控制, 但这些蛋白具体的作用机制目前还不清楚. 为了将来更好地研究DNA磷硫修饰机制, 本文综述了DNA磷硫酰化修饰的发现历程, 特点, 参与DNA磷硫修饰的蛋白结构研究进展, 以及磷硫修饰的DNA作为抗氧化剂研究进展. 同时, 对DNA磷硫修饰机制、生理功能等研究目前所面临的困难, 如硫原子如何渗入DNA骨架, 参与DNA磷硫修饰的五个蛋白是如何协调作用完成DNA磷硫修饰的机理等难题进行了简单概括, 以为相关研究提出一些可能的方向.

关键词: DNA, 磷硫酰化, DndA-E, Dnd表型, 综述

DNA phosphorothioate (PT) modification is a sulfur modification on DNA backbone, in which a non-bridging P—O bond is changed into a non-bridging P-S bond, being the first physiological modification described on the DNA backbone. It is found that the DNA with backbone phosphoration has DNA degradation (Dnd) phenotype upon running electrophoresis in Tris buffer. Moreover, this DNA phosphorothioation belongs to a kind of post-replication modification, where sulfur is incorporated stereo-specifically (i.e., it’s a chiral R_p-type modification, not S_p-type configuration) into DNA backbone at specific sequences. For example, a high frequency of GA was found to be phosphorothioated in Bermanella marisrubri RED65 and Hahella chejuensis KCTC2396, determined by using high pressure or high performance liquid chromatography (HPLC) and mass methods. DNA phosphorothioation is widespread and quantized in bacterial genomes. It was reported that this DNA PT modification is controlled by the five proteins (DndA-E) encoded by dna degradation (dnd) genes cluster (dndA-E) in a sequence found in bacteria and archaea, but the mechanism about how these five proteins function during the pathway of DNA backbone PT modification remains elusive. Among these five genes, four of them, dndA and dndC-E, are essential for the PT modification, while inactivation of dndB resulted in increased phosphorothioation and altered sequence preference. In this paper, we reviewed the discovery history, the features of DNA phosphorothioation modification, and the recent research progresses on the structures and functions of the five proteins involved in DNA backbone phosphorothioation. We also discussed the antioxidant activities of phosphorothioated DNA in biological systems. Finally, for easily understanding the research direction in DNA phosphorothioation, we summarized several questions in the future studies on DNA PT modification, which includes: (1) How sulfur is incorporated into DNA backbone in biological system? (2) How the DNA phosphorothioation is affected by the proteins DndA, DndB, DndC, DndD and DndE? (3) How to get soluble DndB, DndC and DndD in a large quantity? (4) How DndA functions as a cysteine sulfur transferase, because the active site is in a rigid β- sheet conformation?

Key words: DNA, phosphorothioate, DndA-E, Dnd phenotype, review

引用此文

胡中培, 王呈坤, 蓝文贤, 李芳, 曹春阳. DNA骨架磷硫酰化修饰的研究进展[J]. 化学学报, 2013, 71(04): 501-507.

Hu Zhongpei, Wang Chengkun, Lan Wenxian, Li Fang, Cao Chunyang. Recent Advances in DNA Phosphorothioation Modification Studies[J]. Acta Chimica Sinica, 2013, 71(04): 501-507.

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DNA骨架磷硫酰化修饰的研究进展

Recent Advances in DNA Phosphorothioation Modification Studies

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