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Understanding the sequence-dependent DNA damage formation requires probing a complete pool of sequences over a wide dose range of the damage-causing exposure. We used high throughput sequencing to simultaneously obtain the dose dependence and quantum yields for oligonucleotide damages for all possible 4096 DNA sequences with hexamer length. We exposed the DNA to ultraviolet radiation at 266 nm and doses of up to 500 absorbed photons per base. At the dimer level, our results confirm existing literature values of photodamage, whereas we now quantified the susceptibility of sequence motifs to UV irradiation up to previously inaccessible polymer lengths. This revealed the protective effect of the sequence context in preventing the formation of UV-lesions. For example, the rate to form dipyrimidine lesions is strongly reduced by nearby guanine bases. Our results provide a complete picture of the sensitivity of oligonucleotides to UV irradiation and allow us to predict their abundance in high-UV environments., (© 2023. The Author(s).)

Studies on mice exposed to repeated doses of UVR (35 yr ago) and recent epidemiologic investigations and measurements of carcinogenic radiation on patients with nonmelanoma skin cancer showed that repeated doses accumulated. The effects of factors such as genetics, human behavior, kind of skin, variation in intensity of sunlight, etc., cannot be ecaluated quantitatively because of uncertainty. The possibility of inherent indeterminancy must be kep in mind in the study of effects of sunlight.

Various experiments are described which show the locus of action of ultraviolet radiation and of x-ray in delaying cell division of the fertilized egg of Arbacia punctulata to be in the nucleus. Photorecovery following ultraviolet radiation has its locus in the egg cytoplasm. Analogy is drawn with the action of ultraviolet radiation and photorecovery on the E. coli-bacteriophage system, and certain suggestions are made regarding a common mechanism. Photorecovery after x-ray exposure could not be demonstrated.

While our data do not permit us to state the exact locus or mode of action of ultraviolet radiation in the Arbacia egg, certain general conclusions may be reached. The amount of delay of cleavage of these eggs is determined by two principal factors: (1) The extent of an effect, resulting from photochemical action induced by ultraviolet radiation, which is reversible in a biological sense, the reversibility not being directly dependent upon the process of cell division. (2) The sensitivity of the cell division process to the effects of the ultraviolet-induced photochemical reaction. This factor varies with the stage of cell division, the cell being insensitive during a period corresponding to most of mitosis. It seems likely that these findings may apply to cell division in general, but, since the quantitative relationships observed must, in this case, reflect the integration of two semi-independent factors, the over-all picture may appear quite different for different kinds of cells.

The demonstration of five different effects of ultraviolet radiation on the sea urchin's egg indicates that more than one basic photochemical process goes on there. Photorecovery is observed in only one of these. The need for caution in interpreting such effects is obvious. Evidence for a different mechanism for the timing of cleavage in eggs activated by ultraviolet radiation as compared to normally fertilized eggs is presented. The bearing of these studies on survival curves for microorganisms is discussed.

The effect of ultraviolet light in delaying certain events in the cell division cycle has been examined. The time to fusion of the egg and sperm nucleus is not affected by doses of ultraviolet that cause considerable delay in other parts of the cycle. The principal delay occurs before anaphase. Between anaphase and cleavage there is only slight delay. The "refractory period" during which the radiation does not delay the immediate cycle of cell division, does not seem to represent complete refractoriness of the mitotic cycle to interference during this period.

Light of wave lengths 0.30micro to 0.50micro, accelerates return of the cleavage rate of Arbacia eggs to normal, after delay by exposure to ultraviolet radiation (wave lengths 0.238micro to 0.31micro). Recovery is apparently complete. Wave lengths 0.30micro to 0.50micro have no effect on the cleavage rate of normal eggs, nor does such illumination previous to dosage with ultraviolet radiation influence subsequent recovery. Acceleration of recovery of the egg occurs before fertilization as well as after. The effects of ultraviolet radiation and recovery therefrom are essentially the same in nucleated "white halves" as in the intact eggs. This phenomenon in the Arbacia egg seems basically comparable to photoreactivation of bacteria and fungi.