Decoding the role of epigenetic factors in Nucleotide excision repair

Nucleotide excision repair (NER) is one of the most versatile DNA repair pathways in eukaryotic cells that counteract the formation of helix-distorting DNA lesions arising due to UV irradiation, chemical carcinogens and chemotherapeutic drugs. It has been a long-standing question how cells detect and repair lesions in the chromatin environment. Our lab specializes in high resolution mapping of DNA damage (Damage-seq) and DNA repair (XR-seq) at the genome wide level. Our previous work showed faster DNA repair in open and active regions, as opposed to slow repair in heterochromatic and repressed regions in human cells. This suggests the involvement of epigenetic factors in regulating genome structure and function for efficient repair. Central players in chromatin dynamics are histone modifiers. Our preliminary study with histone modifiers reveals the differential effect on damage formation and repair temporally. We aim to identify and decipher the role of novel epigenetic factors in NER using two independent and complementary approaches. First, we will conduct an unbiased CRISPR-cas based genome-wide screen for genes involved in NER. Second, we will conduct in-depth functional studies of candidate epigenetic factors by knocking them out with CRISPR-cas and performing Damage-seq and XR-seq for various types of damages. Our study would shed light on the potential function of the newly discovered epigenetic factors in the repair pathway. In addition, it would open a new avenue of therapeutic potential for cancer treatments by providing foundation to understand their role in cancer.