Nothing is more rewarding than figuring out how proteins, specialized molecular machines, carry out our function. To understand the role of cellular factors in genome maintenance, we are following up our high throughput screens, with molecular biology, cell biology, and biochemistry approaches to decipher at the molecular level the various roles of these novel factors in genome maintenance.
Through our genome-wide screens, we discovered a novel protein complex, which we have named Protexin, that is important for the prevention of genomic instability. Protexin functions by guarding replication forks against the activities of cellular nucleases. This complex is important for the alleviation of cellular pathologies in several replication stress contexts. We are employing biochemical, genetic and cell biology approaches to further understand the role of this complex during replication stress.
Replication – transcription conflicts can pose severe dangers to cellular integrity. Recently, we and others have shown that RNA-DNA hybrids can form as repair intermediates following DNA damage, suggesting a previously unidentified, potentially direct role for RNA polymerase during the replication stress response. This new finding is challenging our basic understanding of DNA repair. In this project, we intend to employ cutting-edge imaging, transcriptomic and molecular biology approaches to understand the role of RNA polymerase following replication stress.