Repairing human DNA damage Scientists have found new clues in plants

, including us humans, are mutated daily by ultraviolet radiation, freekids and other chemicals, causing damage to the DNA of genetic material in the body. In the process of REPAIRing DNA damage, a cross-shaped DNA connection, the Hollidi connection, must be "disassembled" in order for the chromosomes to be properly separated and copied. For now, however, the scientific community has not been able to uncover the working mechanisms behind the dissophase responsible for "dismantling" the work.
recently, a study published in the international journal Nature Chemical Biology by Professor Lin Zhonghui of Fuzhou University's National Joint Local Engineering Research Center for Biopharmacemic Photodynamic Therapy Technology seems to have found new clues. Taking a Hollidi connection dissociation enzyme, MOC1, as the research object, the research group revealed the catalytic mechanism of MOC1 for the first time, which provided important enlightenment to the outstanding substrate specificity recognition mechanism of other species MOC1, and provided important clues for exploring the mechanism of DNA damage repair in human beings." DNA is a double helix-shaped biomass. The basic unit that forms this double helix, the base pair, is like a foundation pillow on a railway, and under the mutage of external electromagnetic radiation, free-forming bases and various chemicals, the bases are interlinked, broken, and structurally altered, resulting in DNA damage. In addition, even without outside interference, the cells themselves make a probability error in the DNA replication process, Lin added.
Lin Zhonghui pointed out that DNA damage, if not repaired in time, will cause the body's genetic information to change, that is, genetic mutations, which can lead to changes in individual physiology and characteristics and even death. In humans, genetic mutations can lead to congenital malformations and cancer. For example, more than 50% of all malignancies found so far carry mutations in the anti-cancer gene p53.
even so, why do most organisms still maintain the stability of their genomes and survive normally? The study found that the body had a security system that could monitor and repair DNA at all times.
Hollidi connection plays an important role in the process, first discovered by British molecular biologist Robin Holliddy in 1964, as a cross-shaped DNA connection formed by the intersection of damaged DNA and template DNA during DNA hoist recombination damage repair.
", after the repair of DNA damage, must be dissofied under the action of MOC1, thus causing the two ionized DNA double strands to be separated and re-established as linear DNA. Therefore, MOC1 is a key enzyme necessary for the normal growth and stable genetic stability of cells including phages, bacteria, fungi, plants and even animals, and is very important for a complete DNA damage repair process, Lin explained.
previous studies have shown that MOC1 can distinguish between linear, trident and cross-shaped DNA and can be specifically combined with Hollidi connections. In addition, the vast majority of MOC1s are "demanding" in the selection of DNA sequences.
differences in the DNA sequence of the "substrate" and even a difference in the base will lead to significant differences in their catalytic efficiency. However, so far, the molecular mechanism of MOC1's selective substrates has not been clear, which hinders our further understanding of MOC1 and the entire DNA damage repair process, Lin said.Science and Technology Daily reporter learned that, in response to the above-mentioned problems, Lin Zhonghui team to plant leafy body MOC1 as the research object, first through a series of bio-chemical experiments to determine the MOC1 specific DNA substrate sequence, and then using X-ray crystallization methods to analyze the MOC1 protein and its complex with DNA substrate crystal structure.
" crystal structures show that the MOC1 protein is highly similar to the phage RUVC in three-dimensional structure, further proving that the leafy carbides are endogenous theorems that originate from photolytic bacteria. The study also revealed that the MOC1 protein has a unique ability, as if hugging the "waist" of MOC1 with one hand, while MOC1's specific identification of DNA sequences is achieved through a conservative base recognition sequence, Lin said.
, the study also found that the active center of MOC1 can bind two metal ions at the same time, relying on bimetallic ion catalysis mechanisms for catalysis. Professor Li Jinyu's team then discovered through molecular dynamics simulation that there was a close relationship between the identification and selection of MOC1 pairs of sequences and the mating of metal ions.
reporter learned that the study combined structural biology, computational biology and biochemistry and other research methods, not only revealed the catalytic mechanism of MOC1, more importantly, but also on how nucleases in the DNA sequence of small differences into their catalytic activity of the huge differences in the scientific problem, innovatively proposed a bimetallic ion-assisted DNA sequence specific selectivity mechanism.
"Although the content of this study is aimed at plant MOC1, because MOC1 catalytic mechanisms are very similar in animals, including us humans, the results of this study will also provide important clues to explore the mechanism of DNA damage repair in humans, and hope to eventually provide some theoretical basis for the fight against related human diseases. Lin Zhonghui said.