RNA Methylation as a Modulator of Cancer Genome Instability
Abstract
The instructions to make, and maintain, a healthy human body are contained in the human genome. This information is encoded in the DNA molecule. While every cell in the human body contains a complete set of instructions, to perform its specific function, each cell uses only a subset of instructions stored in the DNA. The DNA molecule, which can be found in the nucleus of the cell, is part of the chromosome, a complex structure that in addition to DNA includes multiple proteins. The proteins in the chromosome protect the DNA and regulate which pieces of information are extracted by each cell. Information stored in the DNA is retrieved through the production of RNA molecules by mechanisms that copy the information in the DNA so that it can be transported where it needs to be used. RNA molecules carry specific sets of information, such as the blueprints for protein production. Cells are continuously exposed to environmental insults, some of which damage the DNA. Since DNA stores vital information to the cell, multiple mechanisms that detect, and, if possible, repair damaged DNA are present. Breaks in DNA are a common, and dangerous, type of DNA damage. Loss of genomic integrity can transform healthy cells into malignant cancer cells expressing a combination of proteins that promote uncontrolled growth and invasiveness into other tissues. In this proposal, we aim to understand how the different mechanisms that repair DNA damage are regulated, with the objective of targeting these pathways for therapeutic intervention. Recent studies have implicated RNA and proteins that chemically modify RNA as unexpected modulators of DNA repair, but how these mechanisms contribute to DNA repair remains unclear to date. Understanding these processes will undoubtedly reveal a new set of genome integrity mediators that are likely relevant for therapeutic approaches, as RNA, and the proteins that modify RNA represent a novel class of targets for therapeutic drugs. Cancer is a complex malignancy, and a better understanding of the critical processes that repair DNA would allow us to stop proliferation of diseased cells. While loss of DNA integrity promotes the “cancer” state by leading cells to inappropriately use genetic information, it can also be seen as an Achilles’ heel of cancer cells, since presence of DNA damage in cells can lead to cell death. Therefore, cancer cells often become dependent on mechanisms that “repair” DNA in order to survive. Understanding how cells repair DNA is therefore imperative to both prevent cancer formation and interfere with tumor progression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910653
Entities
People
- Pedro Batista
Organizations
- National Cancer Institute
- United States Army