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We have examined the relative sensitivities of different genetic functions to damage induced by u.v. light. For this purpose we have introduced defined amounts of damage into specific regions of the genome of SV40 and have determined the effect of the damage on the survival of transfected viral DNA. We found that the lethal effect of the damage depends on its location within the viral genome. The region most sensitive to damage contains the transcriptional promotors and enhancers for the early and late viral genes plus part of the origin of DNA replication. Lesions within this regulatory region are 3.2-fold more effective in inactivating viral DNA than is the same amount of damage randomly distributed throughout the viral genome. The region least sensitive to damage lies within the coding portion of the viral coat protein genes, which are expressed only late in infection and would therefore be transcribed from undamaged progeny viral genomes, provided DNA replication occurs. Damage within this region is only 45% as effective in inactivating viral DNA as are randomly distributed lesions. Thus there is a 7-fold difference in the lethal effect of DNA damage within the most sensitive and least sensitive regions of the viral genome. Intermediate sensitivities are observed within the transcribed portion of the viral A gene, coding for the T antigen whose expression is required early in infection, and in a region at the terminus of DNA replication. The sum of the individual sensitivities for all regions of the SV40 genome is equal to the total sensitivity of viral DNA subjected to random damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Type

Journal article

Journal

The EMBO journal

Publication Date

01/01/1986

Volume

5

Pages

197 - 203