|Awarded On||February 16, 2022|
|Title||Loss of Site-Specific ADP-ribosylation of Oncohistones in Cancers|
|Award Mechanism||Individual Investigator|
|Institution/Organization||The University of Texas Southwestern Medical Center|
|Principal Investigator/Program Director||W. Lee Kraus|
|Cancer Sites||Breast, Ovary|
Many cancers accumulate mutations in genes that alter the normal activities of the proteins they encode to promote tumor formation and growth. Recently, cancer-causing mutations in genes encoding histone proteins were discovered in a wide array of cancers. We found that some of the mutations in the "oncohistones" disrupt amino acids that are chemically modified by a protein called PARP-1 through a process called ADP-ribosylation (ADPRylation). Loss of ADPRylation in the oncohistones allows the cancer cells to escape growth inhibition mediated by ADPRylation. Moreover, it may also render the cancer cells resistant to the therapeutic effects of PARP inhibitors, a novel class of cancer drug...