DNA-damage repair; the good, the bad, and the ugly

Razqallah Hakem1

  • 1Department of Medical Biophysics, Ontario Cancer Institute/UHN, University of Toronto, Toronto, Ontario, Canada. rhakem@uhnres.utoronto.ca

The EMBO Journal
|February 21, 2008
PubMed

Insights

Impaired DNA repair pathways compromise genomic integrity, leading to severe health issues. This review details functional consequences like cancer and rapid aging from faulty DNA repair mechanisms.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cell Biology

Background:

  • Organisms possess DNA repair pathways and checkpoints to manage DNA damage.
  • Failure of these mechanisms threatens genomic stability.
  • This review examines the functional outcomes of compromised DNA repair.

Purpose of the Study:

  • To review the functional consequences of impaired DNA repair pathways.
  • To highlight the interplay between DNA repair, checkpoints, and cell survival.
  • To understand cellular and organismic impacts of compromised DNA repair.

Main Methods:

  • Review of existing literature on DNA repair pathways.
  • Analysis of functional consequences associated with impaired DNA repair.
  • Integration of DNA repair, checkpoints, and cell survival concepts.

Main Results:

  • Impaired DNA repair leads to compromised genomic integrity.
  • Functional consequences include embryonic lethality, shortened lifespan, and rapid aging.
  • Cancer predisposition is a significant outcome of DNA repair deficiencies.

Conclusions:

  • DNA repair pathways are crucial for maintaining genomic integrity.
  • Deficiencies in DNA repair have profound effects on organismal health and lifespan.
  • Understanding these consequences is vital for addressing genetic instability and associated diseases.

Related Concept Videos

Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
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...
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...
Base Excision Repair01:54

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...