Femtochemistry VII Fundamental Ultrafast Processes in Chemistry, Physics, and Biology A.W. Castleman, Jr. and M.L. Kimble © 2006 Elsevier B.V. All rights reserved 337 Intermediates in the ultrafast repair of DNA by DNA photolyase Zhanjia Hou, Goutham Kodali, Madhavan Narayanan, Kongsheng Yang, and Robert J. Stanley Department of Chemistry, Temple University, Philadelphia, PA 19122 1. Introduction ~:::;+ iii CPD Figure l: x-ray crystal structure of a dodecamer DNA duplex containing a centrally located CPD It is widely known that ultraviolet (UV) light causes DNA damage. The most common form of UV lesion found in DNA is the cis-syn pyrimidine dimer (CPD) in which adjacent pyrimidines on a DNA strand undergo a 2+2 photocycloaddition to generate a cyclobutane ring joining the two rings across the 5- and 6- carbon atoms of the pyrimidine ring. The structure of a thymidine-thymidine CPD lesion has been solved most recently by x-ray crystallography for a dodecamer duplex [1 ]. (See Figure 1). The 5' thymidine of the CPD lesion has a longer hydrogen bond distance to its complementary adenine (2.4 A) than the 3' thymidine (1.9 A). Base stacking is also significantly more disrupted at the 5' end of the CPD, and this may be the motif that causes mutation or regulation problems that lead to disease or death. DNA photolyase is a widely distributed CPD repair protein [2]. It is unique in that it is the only repair protein of its kind that directly reverses the CPD, without excision or backbone modification of the DNA itself.