Abstract
Nucleotide excision repair (NER) is the most versatile DNA repair system of living organisms and the basic reaction is conserved from E. coli to humans. The NER reaction is composed of multi-step processes and can be achieved by ~30 polypeptides in a well-orchestrated manner. The biochemical studies including reconstitution experiments and immunofluorescent studies combined with an elegant technique of micropore UV irradiation have revealed the detailed molecular mechanism of the basic NER reaction. Current interests in this field is to uncover the regulatory mechanism of NER under the more complex environment in living cells and the link between NER and signaling cascades initiated by DNA damage.
We have been working on DDB protein consisting of two subunits, DDB1 and DDB2, which exhibits a high affinity to various types of DNA damage, and demonstrated its stimulatory role in NER especially for CPD. DDB has been recently shown to have another function as a component of E3 ubiquitin ligase and to be implicated in the modification of NER factors as well as histones. On the other hand, we have recently found that in human quiescent cells the NER process can be perturbed at a gap-filling step and the resultant ssDNA gap intermediates initiate the phosphorylation of histone H2AX. These findings provide a new insight into the quality control of DNA repair process that can be perturbed halfway. In this symposium, we will present our recent work and discuss on the regulatory mechanism of NER in human cells.
