ULTRAVIOLET-IRRADIATION PRODUCES NOVEL ENDONUCLEASE III-SENSITIVE CYTOSINE PHOTOPRODUCTS AT DIPYRIMIDINE SITES

Ultraviolet light irradiation of DNA in vitro and in vivo induces cycl obutane dimers, (6-4) pyrimidine-pyrimidone photoproducts and a variet y of minor products. Using a defined DNA fragment, we have identified two classes of sites that can be cleaved by Escherichia coil endonucle ase III: single cytosines whose heat lability corresponds to that of c ytosine hydrates and more heat-stable dipyrimidines containing cytosin e, The dipyrimidine products are induced at sites suggestive of (6-4) photoproducts but are not recognized as (6-4) photoproducts by radioim munoassay, Use of oligonucleotides containing a single cyclobutane thy mine dimer, a (6-4) photoproduct or the Dewar photoisomer of the (6-4) photoproduct also indicated that these products are not substrates fo r endonuclease III, We have therefore identified a minor UV photoprodu ct that has the same sequence specificity as the two major dipyrimidin e photoproducts; it may be a minor isomer, a unique derivative or an o xidative lesion confined to dipyrimidine sites, Its biological signifi cance is not yet known but may be masked by the preponderance of major products at the same sites. Its occurrence at the particular site in dipyrimidine sequences involved in the mutagenic action of UV photopro ducts suggests that it may play a role in generating C to T transition s that are common UV-induced mutations.