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Related Concept Videos

Nucleotide Excision Repair01:38

Nucleotide Excision Repair

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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...
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Overview of DNA Repair02:25

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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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Long-patch Base Excision Repair01:02

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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:
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Base Excision Repair01:54

Base Excision Repair

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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...
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Mismatch Repair01:20

Mismatch Repair

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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...
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Homologous Recombination02:31

Homologous Recombination

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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...
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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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DNA repair pathways in the mitochondria.

Dillon E King1, William C Copeland1

  • 1Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, United States.

DNA Repair
|February 6, 2025
PubMed
Summary

Mitochondrial DNA (mtDNA) maintenance is vital for cellular health, despite limited repair pathways. This review covers mtDNA repair, mutation sources, and its role in cancer.

Keywords:
DNA repairMitochondriaMtDNAMutagenesis

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Area of Science:

  • Mitochondrial biology
  • Genetics
  • Molecular biology

Background:

  • Mitochondria possess a unique circular genome (mtDNA) encoding crucial electron transport chain subunits.
  • mtDNA mutations are linked to various mitochondrial diseases, highlighting the need for genomic integrity.
  • Compared to the nucleus, mitochondria have fewer dedicated DNA repair pathways.

Purpose of the Study:

  • To review mitochondrial DNA repair mechanisms.
  • To discuss sources of mtDNA mutations.
  • To explore the potential role of mtDNA mutagenesis in cancer progression.

Main Methods:

  • Literature review of mitochondrial DNA repair pathways.
  • Analysis of known sources of mitochondrial DNA mutations.
  • Discussion of existing research on mtDNA and cancer.

Main Results:

  • Mitochondria employ various pathways for DNA damage removal and degradation, preventing mutation accumulation.
  • Despite limited repair, specific mechanisms exist to maintain mtDNA integrity.
  • mtDNA mutations arise from diverse sources, impacting cellular function.

Conclusions:

  • Mitochondrial DNA maintenance is critical, with active degradation pathways compensating for fewer repair mechanisms.
  • Understanding mtDNA mutation sources is key to addressing mitochondrial diseases.
  • mtDNA mutagenesis may passively contribute to cancer development.