During the DNA damage response, mammalian RNAP II transcriptional activity is tightly regulated. Much of this regulation has been linked to modifications in the repetitive CTD of the largest subunit of RNAP II. CTD tyrosine phosphorylation increases following DNA damage and is phosphorylated by the proto-oncogene c- Abl. The overall goal of this proposal is to understand the role of tyrosine phosphorylation in the DNA damage response. Defects in the DNA damage response pathway lead to diseases and DNA damage induced apoptosis is the key to chemotherapy and radiation treatment. The specific aims of this proposal include: identifying CTD interacting factors that are regulated by tyrosine phosphorylated CTD through a pull down assay; characterizing these proteins through in vitro and in vivo binding studies; determining the physiological significance of this regulation through various functional assays.