Mismatch repair is a crucial cellular mechanism that identifies and corrects errors that occur during DNA replication, specifically mismatches between complementary base pairs. This process is essential for maintaining the integrity of the genetic code, preventing mutations, and ensuring proper cell function. Mismatch repair works by recognizing mispaired bases, excising the incorrect portion of DNA, and synthesizing the correct sequence to restore fidelity.
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Mismatch repair is a post-replicative mechanism that specifically targets errors made by DNA polymerase during DNA synthesis.
In prokaryotes, the mismatch repair system involves proteins such as MutS, MutL, and MutH that work together to identify and repair mismatches.
In eukaryotes, the mismatch repair system is similar but utilizes different proteins, including MLH1 and MSH2, which are critical for recognizing and fixing errors.
Failure in mismatch repair can lead to microsatellite instability, which is associated with various types of cancer, including colorectal cancer.
The efficiency of mismatch repair can vary among different organisms, with higher fidelity observed in organisms with more complex genomes.
Review Questions
How does mismatch repair function to maintain genetic integrity during DNA replication?
Mismatch repair functions by detecting and correcting base pair mismatches that occur during DNA replication. When DNA polymerase incorporates an incorrect nucleotide, proteins such as MutS recognize the mismatch and recruit other proteins to the site. The incorrect segment of DNA is then excised, and DNA polymerase synthesizes the correct sequence, thereby restoring the accuracy of the genetic code and preventing potential mutations.
Discuss the role of specific proteins in the mismatch repair process and how their dysfunction can lead to disease.
Proteins such as MutS and MutL in prokaryotes or MSH2 and MLH1 in eukaryotes are critical for recognizing mismatches and orchestrating their repair. When these proteins are mutated or dysfunctional, the efficiency of the mismatch repair system decreases. This dysfunction can lead to an accumulation of mutations in the genome, significantly increasing the risk of developing certain cancers, such as those seen in Lynch syndrome due to inherited defects in mismatch repair genes.
Evaluate the implications of mismatch repair on cancer development and its importance in therapeutic strategies.
Mismatch repair plays a vital role in preventing cancer by correcting replication errors that can lead to genomic instability. The loss of functional mismatch repair mechanisms contributes to the development of various cancers, making it a significant area of study for cancer therapies. Understanding how mismatch repair operates allows researchers to explore targeted treatments for cancers associated with its dysfunction, such as using immunotherapy strategies that leverage microsatellite instability as a biomarker for effective treatment plans.
Related terms
DNA polymerase: An enzyme responsible for synthesizing new strands of DNA by adding nucleotides to a growing chain during DNA replication.
MutS: A protein that plays a key role in the initial recognition of mismatched base pairs during the mismatch repair process.
HNPCC (Lynch syndrome): A hereditary condition associated with mutations in mismatch repair genes, leading to an increased risk of certain cancers, particularly colorectal cancer.