Xu Guoliang's research group of Institute of Biochemistry and cell of Chinese Academy of Sciences, in collaboration with several units, published an article in the journal Nature, revealing that vitamin C participates in the production of a new DNA modification

Recently, nature, an authoritative international academic journal, published the research achievement "a vitamin-c-derived DNA modification catalysed by an algal tet homologue" (DOI: 10.1038 / s41586-019-1160-0) jointly completed by Xu Guoliang research group of Institute of Biochemistry and cell biology, Chinese Academy of Sciences It is the first time to identify a new type of Tet homologous protein in Chlamydomonas reinhardtii, a single cell eukaryote It is found that the protein can transfer the carbon skeleton of vitamin C to DNA and produce a new DNA modification In this paper, the reaction mechanism of vitamin C directly involved in the DNA modification was elaborated, and the important role of this protein and its DNA modification in the regulation of photosynthesis of Chlamydomonas reinhardtii was revealed Xu Guoliang's research group has been devoted to the discovery of DNA modifying enzymes and new modifications for a long time, and has carried out in-depth research on DNA modification and its biological functions during DNA demethylation in mammals In eukaryotes, the main form of DNA modification is 5-methylcytosine (5mC) In recent years, three laboratories including Xu Guoliang's research group have found that tet dioxygenase can oxidize 5mC successively to produce 5-hydroxymethylcytosine (5hmc), 5-aldehyde cytosine (5FC) and 5-carboxylcytosine (5cac) The latter two modifications were removed from the genome via thymine DNA glycosidase (TDG) coupled base excision repair or DNA replication to complete DNA demethylation However, the conservation of Tet dioxygenase in the process of evolution, as well as its enzyme activity and function in lower organisms need further exploration (source: nature) in the latest published work, researchers identified eight tet homologous proteins with Chlamydomonas reinhardtii as a model organism Through protein purification and enzyme activity analysis, they found that CR Tet1 can transform 5mC on DNA into two different modified bases, so Cr Tet1 was renamed as CMD1 (5-methylxanthine modification enzyme 1) Further studies show that both of the two new modifications add a glyceryl group to the 5-mc methyl carbon, and they are stereoisomers of each other due to their different spatial structures, so they are named 5-glyceryl-methylcytosine (5-gmc) This is also the eighth DNA base modification found in eukaryotes besides 5mC, 5hmc, 5FC, 5cac, 6mA, 5hmu and base J What's more, when studying the source of glyceryl group on 5gmc, the researchers found that α - ketoglutarate, which is necessary for the traditional dioxygenase reaction, is dispensable in the CMD1 enzyme catalytic reaction and replaced by another very important small molecule: vitamin C Vitamin C not only participates in the catalytic process of CMD1 by providing electrons, but also directly transfers its glycerol group to 5mC methyl carbon to form a new DNA modification The chemical mechanism of CMD1 catalyzing the reaction between 5mC and vitamin C was further analyzed, and glyoxylic acid and carbon dioxide were confirmed as by-products, thus revealing a new enzymatic pathway By developing efficient gene editing methods in Chlamydomonas reinhardtii, the CMD1 mutant strain was obtained The adaptation ability of CMD1 mutant algae to strong light irradiation was obviously weakened, which may be due to the increase of methylation level of some genes caused by the mutation of CMD1, which inhibited the expression of several genes including lhcsr3, which is directly related to the adaptation of strong light, and weakened the negative feedback regulation of light cooperation This work not only reported a new DNA modified 5gmc for the first time, but also reported a new type of enzyme activity reaction mediated by vitamin C, and expounded the important regulatory function of CMD1 and its catalytic product 5gmc in the process of photosynthesis These studies enrich the understanding of the diversity of DNA modification Xue jianhuang, Chen Guodong, Chen Hui and Hao Fuhua of Wuhan Institute of physics and mathematics are the co authors of this paper Researcher Xu Guoliang, Professor Tang Huiru, School of life sciences, Fudan University and researcher Huang kaiyao, Institute of Hydrobiology, Chinese Academy of sciences are co authors There are dozens of research groups involved in this work, including Ding Jianping, Chen Luonan, Institute of Biochemistry and cell, CAS, Liu Wen, Zhu Zhengjiang, Institute of organic science, CAS, Yin Huiyong, Institute of nutrition and health, Ma Weimin, Shanghai Normal University, Elmar Weinhold, RWTH Aachen University, Germany, Rahul M Kohli, University of Pennsylvania, USA This work has been greatly supported by the molecular platform of Institute of Biochemistry and cell, mass spectrometry platform of Institute of plant growth, computational biology experimental technology platform of Mapu Computing Institute, as well as funding support from the Chinese Academy of Sciences, the Ministry of science and technology and the Foundation Committee.