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Mismatch Repair

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

Nucleotide Excision Repair

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

Long-patch Base Excision Repair

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:

Base Excision Repair

Base Excision Repair

One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...

Homologous Recombination

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...

Fixing Double-strand Breaks

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...

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Related Experiment Video

Updated: Aug 14, 2025

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Published on: June 19, 2018

Unexplained mismatch repair deficiency: Case closed.

Ellis L Eikenboom^1,2, Sarah Moen², Lotte van Leeuwen¹

¹Department of Clinical Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 CE Rotterdam, the Netherlands.

|January 10, 2023

Summary

This summary is machine-generated.

Complete Lynch syndrome diagnostics can explain most unexplained MMR-deficient colorectal cancers, often revealing MMR gene involvement. Further research into undetectable variants and VUS interpretation is key to closing these cases.

Keywords:

Lynch syndrome UMMRd colorectal cancer genetic testing unexplained mismatch repair deficiency

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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

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Related Experiment Videos

Last Updated: Aug 14, 2025

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Proofreading and DNA Repair Assay Using Single Nucleotide Extension and MALDI-TOF Mass Spectrometry Analysis

Published on: June 19, 2018

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

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Published on: March 31, 2022

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage

Published on: August 21, 2021

Area of Science:

Oncology
Genetics
Molecular Biology

Background:

DNA mismatch repair (MMR) immunohistochemistry (IHC) is crucial for identifying Lynch syndrome (LS) carriers in colorectal cancer (CRC).
Some MMR-deficient (MMRd) CRCs remain unexplained (UMMRd) even after standard LS diagnostics.

Conclusions:

Comprehensive LS diagnostics, including MMR methylation, germline, and somatic analyses, explain the vast majority of UMMRd CRCs.
UMMRd often indicates MMR gene involvement, potentially with a missed second hit.
Improved detection of undetectable PVs and VUS interpretation are needed to fully resolve UMMRd cases.