DNA damage.

. Name(i) Cause of
DNA
injury Spontaneous damage of DNA molecules (1) Errors in DNA replication DNA replication based on DNA as a template is a rigorous and accurate event, but it is not entirely wrong. Base pairing error frequency is about 10-1-10-2, under the role of DNA replication enzyme base error pairing frequency dropped to about 10-5-10-6, if the replication process is involved in the wrong
nucleotides
, DNA polymerase will also suspend the oxytosis The corrective effect, with its 3'-5' excision
nucleic acid
enzyme activity to remove the wrongly connected nucleotides, and then continue the correct replication, this correction is widely found in the primary and cerete DNA polymerase, can be said to be the correct form of DNA replication errors, thus ensuring the accuracy of replication. However, the corrected misalignment rate is still about 10-10, that is, for every 1010 nucleotides copied there will probably be a base error.(2) Spontaneous chemical changes in DNA Dna DNA molecules in organisms can vary for a variety of reasons, at least for the following types: the four bases in a. base heterogeneously vary from isomer to each other spontaneously (e.g. between oleol and ketone bases) ), this change will make the hydrogen bond between the base pairs change, so that adenine can be equipped with cytosine, thymus can be matched with ostrich, etc. , if these pairs occur in DNA replication, will cause the subgeneration DNA sequence and the generation of DNA different from the wrong damage, as shown in Figure 16-18.16-18 Adenine's rare mutual variants and cytosine (a), or thymus' rare mutual variants and ostrich (b) hydrogen chain formation lead to the next generation of G-C pairings instead of A-T pairings b. base Deamino-acting extracyclic aminos of the base sometimes fall off spontaneously, so that cytosine becomes urine, adenine becomes secondary jaundice (H), ostrich becomes jaundice (X), etc., and when replicated, U and A pairing, H and X are paired with C will lead to the wrong sequence changes in the DNA sequence of the children. The frequency of spontaneous deamino deamino in cytosine is about 190 per cell per day.c. dehydration and deaconing spontaneous hydrolysing can cause radon and ion to fall off the ribosphoric acid skeleton of the DNA chain. A mammal cell spontaneously sheds about 1000 radon on the DNA chain within 20h at 37 degrees C, and about 500 radon: it is estimated that a long-lived mammal cell (such as nerve cells) spontaneously dislodges about 108 during the entire life, accounting for about 3% of the total number of radon in the cell DNA.d. Base modification and chain fracture cell breathing by-products O2, H2O2, etc. will cause DNA damage, can produce thyroid glycol, hydroxymethane and other base modifications, but also may cause DNA single-stranded fracture and other damage, each mammal cell daily DNA single-stranded rupture occurred about 50,000 times. In addition, DNA methylation, other structural changes, etc. can occur in the body, the accumulation of these injuries may lead to aging., if cells do not have efficient repair systems, the mutation rate of organisms will be greatly increased.. 2. DNA damage caused by physical factors Rays is the most noticeable.16-19 Thymosin thymosin thymosin djupolymer formation (1) UV-induced DNA molecular damage began as early as the study of the effects of UV rays. When DNA is most susceptible to ultraviolet light at its absorbent wavelength (-260nm), it is mainly the entergens adjacent to the same DNA chain connected to a djumer by co-price bonds, and two adjacent Ts, or two Cs, or between C and T can be cyclobutane ring in two polymers, the most easily formed is the TT djumer, as shown in Figure 16-19.people's skin is exposed to ultraviolet light to form a dmneuvial frequency of up to 5×104/cell per hour, but only confined to the skin, because ultraviolet light can not penetrate the skin. However
microorganisms
affect their survival when exposed to ultraviolet light. Ultraviolet radiation can also cause damage such as broken DNA strands.(2) DNA damage caused by ionizing radiation Ionizing radiation damage DNA has direct and indirect effects, the direct effect is that DNA directly absorbs ray energy and is damaged, indirect effect refers to other molecules around the DNA (mainly water molecules) absorb ray energy to produce a highly reactive freelance base and thus damage DNA. Ionizing radiation can lead to a variety of changes in DNA molecules: a. base changes are mainly caused by OH-free fundamentals, including base oxidation modification on DNA strands, peroxide formation, base ring destruction and shedding. In general, the sorghum is more sensitive than the radon.b. DNA changes Every carbon atom on DNA and hydrogen on hydroxyl can react with OH-, causing DNA to break down and eventually causing DNA strands to break.c.DNA chain fracture This is a serious injury event caused by ionizing radiation, and the number of broken chains increases with the dose of exposure. Both the direct and indirect effects of the rays can cause DNA strands to break by damaging DNA or breaking the phosphate bonds. A chain break in a DNA double strand is called a single strand break, and a DNA double strand break is called a double strand break in the same place or similar. Although single-stranded fractures occur 10-20 times more frequently than double-stranded fractures, they are easier to repair;d.crosslinking includes DNA stranding and DNA-
protein
crosslinking. The same DNA chain or between the bases on the two DNA strands can be co-priced bond binding, DNA and proteins will also be connected by co-priced bonds, histones, chromatin non-histones, regulatory proteins, and replication and transcription-related enzymes will be connected to DNA co-priced bonds. These crosslinks are the molecular basis for chromosomal distortions seen by cells under
micromoscopy
after they are exposed to ionizing radiation, affecting cell function and DNA replication.. 3. DNA damage caused by chemical factors The understanding of DNA damage caused by chemical factors first came from the study of chemical weapons lethality, and the later research on the effects of chemotherapy and chemical carcinogens on cancer has made people pay more attention to the effects of mutants or carcinogens on DNA.(1) damage to DNA Alkylizer is a class of pro-electron compounds that can easily react with the pro-nuclei of large molecules in organisms. The agent's effect can cause various types of DNA damage:a. base alkylation. The alkyl can easily be added to the DNA chain on the N or O of the cytosine, wherein the N7 of the ostrich and the N3 of the adenine are the most vulnerable, the alkylated alkaloid base pairing will change, for example, the ostrich N7 is alkalized and no longer paired with the cytosine, but with the thymus pairing, the result will be G-C into A-T. b. Base shedding. The glycoside bonds of alkylated ostrich are unstable and easy to fall off to form baseless bits on DNA, and any nucleotides can be inserted during replication, resulting in a change in sequence. c. Break the chain. Oxygen on the DNA chain's phosphate bonds is also easy to be alkanized, resulting in unstable triglyceride bonds, easy to hydrolysate between sugar and phosphoric acid, so that the DNA chain breaks. d. Interlinking. There are two types of alkyl agents, one is single-functional alkyl agents, such as methyl methane iodide, can only make one bit of alkylation, the other is a dual-functional alkyl agents, chemical weapons such as nitrogen mustard, sulfur mustard, some anti-cancer drugs such as cyclophosphamide Some carcinogens such as nitrosamines, such as ethylene nitrosamines, are among them, and their two functional foundations can make two alkylations at the same time, resulting in interlinkages between DNA strands, DNA strands, and DNA and proteins. 16-20 Nitrogen mustard causes DNA molecules to crosslink (a) near the intersection of two strands of DNA molecules on the ostrich ; Damage Artificial can be synthesized into a number of base-like substances used as mutation-promoting agents or anticancer drugs, such as 5-bromouriacine (5-BU), 5-fluorouracil (5-FU), 2-amino adenine (2-AP) and so on. Because its structure is similar to the normal base, the entry cell can replace the normal base into the DNA chain and interfere with DNA replication synthesis, for example, the 5-BU structure is very similar to the thymus, in the ketone structure paired with A, but more likely to become an oleol structure paired with G, in DNA replication led to A-T conversion to G-C. There are also chemicals present in synthetic or environmental conditions that can specifically modify the base on the DNA chain or alter the base sequence by affecting DNA replication, such as nitrites that can turn C deaminate into U, which can turn G on DNA into an A pair; (ii) consequences of DNA damage the above damage eventually leads to changes in the molecular structure of DNA, a mutation at the molecular level of DNA that is the basis for the overall genetic mutation. the final changes in molecules after DNA damage, there are several types: 1. point mutation refers to the variation of a single base on DNA. Substitutes for radon (the mutual substitution between A and G), substitutes for c and T are called transitions, and transvertion is called transvertion. . 2. Deletion refers to the disappearance of one or more nucleotides on the DNA strand. . 3. Insertion refers to the insertion of one or a nucleotide into a DNA strand. In a protein-encoded sequence where the number of missing and inserted nucleotides is not an integer of 3, a reading frame shift occurs, confusing the
amino acid
sequence that is later translated, called the frame shift mutate. . 4. Inverting or transposition refers to the recombination of the DNA chain so that one of the nucleotide strands is reversed or migrated from one place to another. . 5. Double-stranded fracture has been, as mentioned above, a double-stranded fracture of monoplex cells is a fatal event. mutations or mutagenics can have four consequences for organisms: (1) lethality, (2) loss of certain functions, and (3) alteration of the
gene
type (genotype) without changing the phenotype ;(4) resulting in species-friendly results that allow the organism to evolve.


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