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Alterations in chromatin structure during DNA excision repair
Summary
Mammalian cells undergoing DNA repair show initial changes in chromatin structure. Over time, repair synthesis becomes resistant to nuclease, suggesting chromatin reorganization during the repair process.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Recent studies indicate chromatin structure changes during DNA excision repair in mammalian cells.
- DNA repair synthesis is initially sensitive to nuclease but becomes resistant over time.
- This phenomenon involves the redistribution of nucleotides incorporated during repair.
Purpose of the Study:
- To investigate the dynamic changes in chromatin structure during DNA excision repair.
- To present models explaining the observed alterations in nucleosome-associated DNA during repair.
- To discuss recent data supporting or refuting proposed models.
Main Methods:
- Excision repair assays in mammalian cells (human and African green monkey).
- Damage induction using chemical agents (N-acetoxy-2-acetylaminofluorene, 7-bromomethylbenz[a]anthracene, angelicin) and ultraviolet radiation.
- Assessment of nuclease sensitivity of newly synthesized DNA during repair.
Main Results:
- Newly incorporated nucleotides during excision repair are initially sensitive to staphylococcal nuclease.
- Over time, these nucleotides become nuclease-resistant and associate with nucleosome-core-length DNA.
- This rearrangement of repair synthesis products within chromatin is observed across different cell types and damaging agents.
Conclusions:
- Excision repair involves dynamic alterations in chromatin organization.
- Two models, nucleosome unfolding/refolding and sliding of core proteins, are proposed to explain these changes.
- Further investigation is needed to elucidate the precise mechanism of chromatin rearrangement during DNA repair.