Genetics

What is Dna Mismatch Repair



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DNA is the genetic material of human cells. The sequence is made of four nucleotides that pair with one another via hydrogen bonds in the center of the double helix. The four nucleotides are adenine, guanine, thymine, and cytosine. Adenine is always paired with thymine, and guanine is always paired with cytosine. A fifth base, uracil, is found in RNA, replacing thymine. RNA is transcribed from the DNA sequence and is the blueprint for protein production in the cell.

DNA Errors of Replication

If uracil is inserted into the DNA strand during replication instead of thymine, a repair mechanism called base excision repair, or BER, removes the uracil so DNA polymerase can replace it with thymine in a manner identical to DNA replication - basically allowing the process to be redone after the error. The recognition of this error is accomplished by an enzyme called DNA glycosylase that specifically recognizes and removes the uracil. If a mismatched base is present, for example a cytosine paired with adenine, the hydrogen bonding between the two nucleotides disrupted and the altered conformation is recognized as an error, or damage. The mismatch repair mechanism was first seen and studied in E. coli, a bacteria common in our environment.

The Mismatch Repair Mechanism

Mismatch repair shares enzymes with the other repair pathways, namely base excision (BER) and nucleotide excision repair (NER). A protein encoded by the MSH genes recognizes the mismatch, and an enzyme encoded by the MLH (or PMS) genes takes the lead in cutting out the wrongly placed base. The empty space in the DNA is patched by DNA polymerase, similar to DNA replication.

The mismatch repair mechanism is also one tool the cell uses to review the results of crossover during meiosis, called homologous recombination.

The Effect of No Mismatch Repair

If wrongly paired bases are not removed from the DNA strand, future strands may have the mutation incorporated. Mutations may alter the final protein product, or even result in a lack of protein. This disrupts cellular function.

Mutations in the MSH2 and MLH1 genes have been associated with colon cancer, hereditary non-polyposis colon cancer (HNPCC). The findings regarding these genes have placed them in the category of tumor suppressor genes, meaning that a lack of their expression and/or function leads to cancer formation. Other genes also need to be mutated before the cancer manifests due to redundant proteins, a common theme in evolutionary development to protect the organism. Redundancy makes a particular gene non-essential, allowing some mutation to be non-damaging to the organisms as a whole.

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