DNA repair during organogenesis

Robert K Vinson1, Barbara F Hales

  • 1Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, Que., Canada H3G-1Y6.

Mutation Research
|November 13, 2002
PubMed

Insights

DNA repair pathways are crucial for maintaining genomic stability during mammalian organogenesis. Their complex regulation and developmental stage-specific expression highlight their importance in preventing malformations from genotoxic damage.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background:

  • Genotoxic agents can damage DNA, impacting cellular processes and gene expression.
  • DNA repair pathways are essential for maintaining genomic integrity, with defects leading to human syndromes.
  • Understanding DNA repair during development is critical for preventing congenital abnormalities.

Purpose of the Study:

  • To review the expression and activity of DNA repair pathways during mammalian organogenesis.
  • To explore the role of DNA repair in the conceptus's response to genotoxic agents.
  • To examine the regulation and importance of DNA repair during embryonic development.

Main Methods:

  • Review of scientific literature on DNA repair pathways and mammalian organogenesis.
  • Analysis of gene expression, protein levels, and activity of repair pathways during development.
  • Examination of cell cycle checkpoint pathways activated by genotoxic stress.

Main Results:

  • Key DNA repair pathways (nucleotide excision repair, base excision repair, mismatch repair, recombination repair) are expressed during organogenesis.
  • Genotoxic stress-activated cell cycle checkpoint pathways are also present.
  • Developmental-stage-specific alterations in DNA repair pathway expression and activity indicate complex regulation.
  • Disruption of DNA repair pathways significantly impacts development, demonstrating their critical role.

Conclusions:

  • DNA repair pathways are vital for genomic stability during mammalian organogenesis.
  • The conceptus has a limited ability to modify DNA repair responses to genotoxic agents.
  • Proper functioning of DNA repair is essential for normal embryonic development and preventing malformations.

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...
Nucleotide Excision Repair01:46

Nucleotide Excision Repair

Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. Damaged DNA can be detected and repaired in a process called nucleotide excision repair (NER). NER employs a set of specialized proteins that first scan DNA to detect a damaged region. Next, NER proteins separate the strands and excise the damaged area. Finally, they coordinate the replacement with new, matching nucleotides.DNA distortion and damageCells are...
Nucleotide Excision Repair01:46

Nucleotide Excision Repair

Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. Damaged DNA can be detected and repaired in a process called nucleotide excision repair (NER). NER employs a set of specialized proteins that first scan DNA to detect a damaged region. Next, NER proteins separate the strands and excise the damaged area. Finally, they coordinate the replacement with new, matching nucleotides.DNA distortion and damageCells are...
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.
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Fixing Double-strand Breaks02:04

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...