Cancer is a genetic disease caused by mutations in DNA, the material that stores our genetic information. Accessing this information correctly is essential for human health and relies on proteins that interact with and regulate chromatin, the organizational hubs of the genome. DNA within each of our cells is damaged thousands of times per hour per day, which can lead to mutations, decreased genome integrity and ultimately cancer. We have discovered that a large family of human proteins called bromodomain (BRD) proteins, which connect chromatin to DNA processes, are genome protectors and suppressors of DNA damage and cancer. Understanding the basic biology of these proteins is essential for g...
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Cancer is a genetic disease caused by mutations in DNA, the material that stores our genetic information. Accessing this information correctly is essential for human health and relies on proteins that interact with and regulate chromatin, the organizational hubs of the genome. DNA within each of our cells is damaged thousands of times per hour per day, which can lead to mutations, decreased genome integrity and ultimately cancer. We have discovered that a large family of human proteins called bromodomain (BRD) proteins, which connect chromatin to DNA processes, are genome protectors and suppressors of DNA damage and cancer. Understanding the basic biology of these proteins is essential for guiding efforts to develop drugs targeting these proteins and translating this work into the clinic. We focus on BRD proteins as they are highly mutated in cancer and represent emerging cancer therapeutic targets. Our goal with this project is to define how BRD proteins maintain DNA integrity through replication and transcriptional stress response pathways and to determine the involvement of these pathways in cancer. We hypothesize based on our research that BRD protein deficiencies in cancer promote this disease by inducing DNA damage, which may provide a vulnerability that can be targeted therapeutically. By understanding how BRD proteins suppress DNA damage and promote genome integrity, we can start to address this idea. Here, we will determine the role of BRD proteins in replication and transcription stress responses, known contributors to mutations and cancer development. Success of this project will define the involvement of BRD proteins in genome integrity and tumor suppression pathways in cancer, information likely to inform the development and use of therapeutics targeting BRD proteins and their deficiencies in cancer.
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