DNA!!!!!! how does the cell repair DNA damaged by mutagens??? i would like to know step by step if possible?

Question

could anyone please explain?

Answer 1

Photoreactivation

This is one of the simplest and perhaps oldest repair systems: it consists of a single enzyme which can split pyrimidine dimers (break the covalent bond) in presence of light. Click here to see the photoreactivation reaction.

The photolyase enzyme catalyzes this reaction; it is found in many bacteria, lower eukaryotes, insects, and plants. It seems to be absent in mammals (including humans). The gene is present in mammals but may code for a protein with an accessory function in another type of repair.

2. Ligation of single strand breaks

X-rays and some chemicals like peroxides can cause breaks in backbone of DNA. Simple breaks in one strand are rapidly repaired by DNA ligase. Microbial mutants lacking ligase tend to have high levels of recombination since DNA ends are recombinogenic (very reactive). A human known only by the code name of 46BR was found to have mutations in both of her DNA ligase I genes; she had poor growth, immunodeficiency, and sun sensitivity and died at a young age of lymphoma. Fibroblast cells from 46BR are sensitive to killing by DNA damaging agents including ionizing radiation. In addition, the rare hereditary disease Bloom syndrome also somehow is involved with DNA ligase deficiency (although the Bloom syndrome protein is a DNA helicase); patients' cultured cells have high levels of chromosome aberrations and spontaneous mutation.

B. Damage removal

1. Base excision repair

The damaged or inappropriate base is removed from its sugar linkage and replaced. These are glycosylase enzymes which cut the base-sugar bond. example: uracil glycosylase--enzyme which removes uracil from DNA. Uracil is not supposed to be in DNA--can occur if RNA primers not removed in DNA replication or (more likely) if cytosine is deaminated (this is potentially mutagenic). The enzyme recognizes uracil and cuts the glyscosyl linkage to deoxyribose. The sugar is then cleaved and a new base put in by DNA polymerase using the other strand as a template. Mutants lacking uracil glycosylase have elevated spontaneous mutation levels (C to U is not fixed, which leads to transitions) and are hyper-sensitive to killing and mutation by nitrous acid (which causes C to U deamination).

There are other specific glycosylases for particular types of DNA damage caused by radiation and chemicals.

2. Mismatch repair

This process occurs after DNA replication as a last "spellcheck" on its accuracy. In E. coli, it adds another 100-1000-fold accuracy to replication. It is carried out by a group of proteins which can scan DNA and look for incorrectly paired bases (or unpaired bases) which will have aberrant dimensions in the double helix. The incorrect nucleotide is removed as part of a short stretch and then the DNA polymerase gets a second try to get the right sequence.

Human mismatch repair proteins have recently been identified and are very similar to those of the prokaryote E. coli and the simple eukaryote yeast (this is an old invention of cells); mutations are found to be passed in the germline of families with some types of inherited colon cancer (HPNCC).

3. Nucleotide excision repair

This system works on DNA damage which is "bulky" and creates a block to DNA replication and transcription (so--UV-induced dimers and some kinds of chemical adducts). It probably recognizes not a specific structure but a distortion in the double helix. The mechanism consists of cleavage of the DNA strand containing the damage by endonucleases on either side of damage followed by exonuclease removal of a short segment containing the damaged region. DNA polymerase can fill in the gap that results. Excision repair is shown here .

Mutants that are defective in NER have been isolated in many organisms and are sensitive to killing and mutagenesis by UV and chemicals which act like UV. Humans with the hereditary disease xeroderma pigmentosum are sunlight-sensitive, they have very high risks of skin cancers on sun-exposed areas of the body and have defects in genes homologous to those required for NER in simple eukaryotes. NER mutants in lower organisms are UV-sensitive and have elevated levels of mutation and recombination induced by UV (because they are unable to use the accurate NER method to remove pyrimidine dimers and must use mutagenic or recombinogenic systems).

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