Drosophila Melanogaster is an extensively used model system in the scientific community. It has been traditionally used to study ionizing radiation and chemical induced mutagenesis, double strand break repair and recombination. Despite these extensive work in these research areas, there are only limited number of studies on nucleotide excision repair in this vital model organism. An early study from 1990s has reported that Drosophila cannot perform the transcription-coupled repair pathway of nucleotide excision repair mechanism. This conclusion was later seemingly supported by the Drosophila genome sequencing project which was unable to identify any homologs to CSA and CSB genes, which are known to be required for transcription-coupled repair in mammals and yeast. In this project, by using XR-Seq genome-wide repair mapping technology, we have found that Drosophila can perform transcription-coupled repair both in vitro and in vivo systems, including 4 different developmental stages, 2 genders and 3 organs, at comparable levels to human cells. This project has also identified that contrary to humans and other multicellular organisms that are previously studied, in Drosophila, the XPC repair factor is required for both the global repair pathway and the transcription-coupled repair pathway. This necessity of XPC in the Drosophila nucleotide excision repair mechanism is similar to the behavior of respective XPC genes in Saccharomyces cerevisiae and Schizosaccharomyces pombe, in which XPC mutants are totally deficient in nucleotide excision repair mechanism.