Mismatch repair

Definition

Mismatch repair is a crucial DNA repair mechanism that corrects base-pairing errors that occur during DNA replication. This process enhances genomic stability by identifying and repairing mismatched nucleotides, thus preventing the accumulation of mutations that can lead to diseases like cancer. By ensuring accurate DNA replication, mismatch repair plays a significant role in maintaining cellular integrity and reducing the risk of genotoxic effects.

5 Must Know Facts For Your Next Test

1. Mismatch repair primarily targets errors that escape proofreading during DNA replication, such as nucleotide substitutions and small insertions or deletions.
2. The process involves several key proteins, including MutS, MutL, and MutH, which work together to detect, excise, and replace mismatched nucleotides.
3. Deficiencies in mismatch repair systems can lead to hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, which increases cancer risk significantly.
4. In addition to correcting replication errors, mismatch repair also plays a role in preventing genetic instability induced by environmental factors and certain chemicals.
5. The mismatch repair pathway operates in both prokaryotic and eukaryotic cells, highlighting its fundamental importance in cellular processes across different life forms.

Review Questions

• How does the mismatch repair system identify and correct errors during DNA replication?
  • The mismatch repair system identifies errors by recognizing mismatched base pairs that do not fit properly in the DNA helix. Key proteins like MutS bind to the mismatched region, signaling for other proteins such as MutL and MutH to assist in excising the incorrect nucleotide. This coordinated effort ensures that the error is replaced with the correct base, thus maintaining the fidelity of DNA replication.
• Discuss the implications of deficiencies in mismatch repair on human health, particularly regarding cancer risk.
  • Deficiencies in mismatch repair mechanisms can lead to an accumulation of mutations in critical genes, which significantly increases the risk of developing various cancers, most notably colorectal cancer. Conditions such as Lynch syndrome arise from inherited mutations in mismatch repair genes, leading to a predisposition for tumors at multiple sites. Understanding these implications underscores the importance of effective mismatch repair in preventing genomic instability and associated diseases.
• Evaluate the role of mismatch repair in the context of genotoxicity and its broader significance in toxicology.
  • Mismatch repair is vital in mitigating genotoxicity by correcting DNA replication errors that could otherwise result in harmful mutations. By efficiently repairing these errors, the mismatch repair system reduces the likelihood of developing mutations that contribute to cancer and other genetic disorders. In toxicology, understanding how exposure to environmental agents affects this repair mechanism is crucial for assessing risks associated with genotoxic substances and developing strategies for prevention and treatment.

Related terms

DNA polymerase: An enzyme responsible for synthesizing new DNA strands by adding nucleotides to a growing chain during DNA replication.

Heteroduplex: A double-stranded DNA molecule formed by the pairing of strands from different sources, which can lead to mismatches if not properly repaired.

Exonuclease: An enzyme that removes nucleotides from the ends of a DNA strand, often used in the mismatch repair process to excise incorrect bases.