Mismatch repair

Definition

Mismatch repair is a DNA repair system that corrects errors that occur during DNA replication, specifically those that involve incorrectly paired nucleotides. This system plays a crucial role in maintaining the integrity of the genetic information by identifying and repairing mismatches, which helps prevent mutations that could lead to diseases such as cancer. Proper functioning of mismatch repair is vital not just for the accuracy of DNA replication, but also in the context of cellular response to DNA damage.

5 Must Know Facts For Your Next Test

1. Mismatch repair primarily functions to correct base-pairing errors that escape proofreading by DNA polymerases during replication.
2. The mismatch repair process involves several key proteins, including MutS, which recognizes the mismatch, and MutL, which coordinates the repair process.
3. In humans, defects in mismatch repair genes can lead to hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome.
4. The repair process typically involves removing a segment of the newly synthesized DNA strand containing the mismatch and resynthesizing it using the template strand as a guide.
5. This system is crucial for reducing the mutation rate in cells, thus preserving genomic stability and preventing the accumulation of mutations over time.

Review Questions

• How does mismatch repair improve the fidelity of DNA replication, and what role do key proteins play in this process?
  • Mismatch repair enhances the fidelity of DNA replication by correcting base-pairing errors that might otherwise escape the proofreading ability of DNA polymerases. Key proteins like MutS detect mismatched bases, while MutL coordinates the subsequent steps needed to excise and replace the incorrect nucleotides. By ensuring that errors are promptly fixed, this mechanism significantly reduces the likelihood of mutations entering the genetic material.
• Discuss the implications of defective mismatch repair systems in humans and how they relate to certain diseases.
  • Defective mismatch repair systems in humans are linked to various diseases, most notably hereditary nonpolyposis colorectal cancer (HNPCC). When mismatch repair genes are mutated or dysfunctional, it leads to an increased mutation rate within cells. This accumulation of mutations can disrupt normal cellular processes and promote tumorigenesis, illustrating the critical role of this repair mechanism in maintaining genomic stability and preventing cancer development.
• Evaluate how understanding mismatch repair mechanisms can influence cancer treatment strategies and genetic research.
  • Understanding mismatch repair mechanisms can significantly impact cancer treatment strategies by identifying patients who may benefit from targeted therapies based on their genetic profiles. For instance, tumors with defective mismatch repair may respond differently to certain chemotherapeutic agents compared to those with functional systems. Moreover, insights into these pathways can guide genetic research aimed at developing novel interventions or preventative measures for individuals at high risk for conditions associated with mismatch repair deficiencies.

Related terms

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

Nucleotide Excision Repair: A DNA repair mechanism that removes bulky DNA lesions and replaces them with correctly synthesized DNA.

MutS Protein: A protein that detects and binds to mismatched bases in the DNA, initiating the mismatch repair process.