The Role of PARP3 in the Formation of Chromosomal Translocations
Cancer cells have many abnormalities in their DNA. In a cell, DNA is divided into large structures called chromosomes. Chromosomes can be broken as a result of exposure to damaging environmental factors such as sunlight or cancer treatments such as chemotherapy. Broken chromosomes are very dangerous to the cell because essential genetic information can be lost or corrupted, ultimately resulting in death of the cell. Ideally, a cell with broken chromosomes is able to correctly rejoin the broken ends to restore the chromosomes to their original form. However, occasionally cells mix up the broken ends and incorrectly join chromosomes, forming a hybrid chromosome known as a translocation. Translocations can lead to abnormal cell growth that can progress to cancer. Translocations contribute to the development of many pediatric cancers of the blood, bone and brain. In addition, translocations are found in cancers that result from chemotherapies that cause chromosome breakage. Despite the central role that translocations play in pediatric cancer, very little is known about how they form.
We have identified a novel gene, PARP3, that is important for the formation of translocations. We propose to determine the role of PARP3 in promoting translocations by identifying other factors that interact with PARP3 and studying how PARP3 binds to broken chromosomes. Understanding how translocations occur could foster the development of therapies to limit translocations thereby suppressing the formation of cancer.