Critical DNA damaging pathways in tumorigenesis.

Jake A Kloeber1, Zhenkun Lou2

  • 1Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA; Mayo Clinic Medical Scientist Training Program, Mayo Clinic, Rochester, MN, 55905, USA.

Summary

DNA damage is a key driver of cancer development. Understanding DNA repair and damage responses offers new therapeutic strategies for targeting cancer vulnerabilities.

Related Concept Videos

Nucleotide Excision Repair01:38

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...
4.3K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
39.4K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.6K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.8K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.5K
Overview of DNA Repair02:25

Overview of DNA Repair

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.
Chemically...
32.5K