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DNA repair in specific sequences in mammalian cells
1Department of Biological Sciences, Stanford University, CA 94305-5020.
Journal of Cell Science. Supplement
|January 1, 1987
Summary
DNA repair efficiency depends on DNA sequence activity and chromatin structure. Active genes are repaired preferentially, while condensed heterochromatin shows deficient repair of bulky adducts but not specific base damage.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA repair mechanisms are crucial for maintaining genomic integrity.
- Chromatin structure, particularly heterochromatin, can influence DNA accessibility and repair.
- Gene activity is known to correlate with differential DNA repair rates.
Purpose of the Study:
- To investigate how DNA sequence function and activity impact DNA repair efficiency.
- To determine if chromatin condensation in heterochromatin affects the repair of various DNA adducts.
- To examine the preferential repair of pyrimidine dimers in active genes across different species.
Main Methods:
- Studied excision repair of DNA adducts in heterochromatic alpha DNA of monkey cells.
- Assessed pyrimidine dimer removal in specific genes of rodent and human cells using a dimer-specific endonuclease.
- Analyzed repair synthesis following exposure to various DNA-damaging agents (UV, gamma rays, chemical mutagens).
Main Results:
- Heterochromatic alpha DNA showed severely deficient removal of bulky adducts (psoralen, aflatoxin B1, N-acetoxyacetylaminofluorene) but proficient repair of thymine glycols and UV-induced damage.
- UV treatment enhanced repair of bulky adducts in alpha DNA, suggesting chromatin structure alteration.
- Active genes (DHFR, c-abl) exhibited preferential and efficient pyrimidine dimer removal compared to non-transcribed regions or the overall genome.
- Repair deficiency in XP-C cells was observed in both active genes and the overall genome, indicating a role for specific repair pathways.
Conclusions:
- Highly condensed chromatin in heterochromatin hinders repair of bulky DNA adducts, while repair of specific base damage and UV damage is less affected.
- DNA repair is preferentially directed towards active genes, suggesting that genomic stability is prioritized in essential sequences.
- Resistance to DNA damage and mutagenic efficiency may be better correlated with the repair status of active genes than with overall genome repair levels.