Transcription-Coupled DNA Repair
Our lab is part of a large NCI funded project in Structural Biology of DNA Repair that aims at producing biologically relevant DNA repair structures and identifying fundamental structural principles for repair proteins. The role of electron microscopy is to provide structures of large macromolecular complexes involved in these processes that complement the X-ray crystallographic structures of individual components. Of special interest to us is the mechanism of transcription-coupled DNA repair (TCR), and the role of human TFIIH and RNA Pol II in this process. In collaboration with the Cooper (LBNL) and Mitra labs (UTMC), we have tested human Pol II and TFIIH produced in my lab for binding to XPB, CSB and additional TCR proteins (Sarker et al., Mol. Cell 2005). We have also produced a 3-D reconstruction of human Pol II by cryo-EM showing distinctive features with respect to the yeast crystal structure. Our future plans are to produce structures of TCR supracomplexes in the context of the damaged DNA.