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Identification of ultraviolet-inducible proteins that bind to a TGACAACA sequence in the polyoma virus regulatory
1Comprehensive Cancer Center, Columbia University, New York, New York 10032.
Abstract:
The exposure of mammalian cells to UV light or other DNA-damaging agents induces several responses which may provide cellular defense mechanisms and also play a role in carcinogenesis. Employing a 257-base pair DNA fragment from the polyoma virus that contains the origin of replication and regulatory region of this virus, we have identified a set of DNA-binding proteins that are induced in normal rat fibroblasts at 6-24 h after UV exposure. These proteins bind to a specific octamer sequence (TGACAACA) designated the "UV response element." Purification of these inducible proteins on a UV response element affinity column revealed a set of proteins, among which the major protein has a molecular weight of 40,000, which co-purify with c-fos but do not react with antibodies to c-jun-encoded proteins. These UV-induced proteins may, in concert with other cellular components, play a role in mediating specific cellular responses to DNA damage in mammalian cells.
Insights
Exposure to UV light induces DNA-binding proteins in mammalian cells that respond to DNA damage. These proteins may play a role in cellular defense and carcinogenesis.
Area of Science:
- Molecular biology
- Cellular response to DNA damage
- Carcinogenesis
Background:
- Mammalian cells exhibit defense mechanisms against DNA damage from agents like UV light.
- These responses are crucial for cellular integrity and can influence cancer development.
Purpose of the Study:
- To identify DNA-binding proteins induced by UV radiation in mammalian cells.
- To characterize the binding specificity and molecular properties of these UV-induced proteins.
Main Methods:
- Utilized a polyoma virus DNA fragment containing replication origin and regulatory regions.
- Employed UV-irradiated normal rat fibroblasts.
- Applied UV response element affinity chromatography for protein purification.
Main Results:
- Identified a set of DNA-binding proteins induced 6-24 hours post-UV exposure.
- These proteins bind to a specific octamer sequence (TGACAACA), termed the "UV response element."
- The major purified protein (40,000 MW) co-purifies with c-fos but not c-jun proteins.
Conclusions:
- UV-induced proteins binding to the UV response element are identified.
- These proteins may mediate cellular responses to DNA damage.
- Potential role in cellular defense and carcinogenesis warrants further investigation.
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