Molecular basis of gynecological oncology – TopBP1 protein and its participation in the transcription process

Abstract

Breast and ovarian cancer are among the most common malignancies of women in the world. About 5 – 10% of the cases are considered familial. Germline mutations in the BRCA1 and BRCA2 genes are strong predictors of breast and/or ovarian cancer development. However, currently known susceptibility genes including BRCA1, BRCA2, ATM, Chk2, PALB2, and BRIP1 explain less than 25% of familial breast and/ovarian cancers. Other genes, such as TopBP1 are also likely to be involved in hereditary predisposition to breast and/or ovarian cancer. TopBP1 protein displays structural and functional similarities with BRCA1, and these two proteins have been suggested to function partially in the same cellular processes. TopBP1 protein is involved in DNA repair and cell cycle checkpoint control. Moreover, TopBP1 interacts with transcription factors, such as E2F1, p53, Miz-1, HPV16 E2, and regulates their activity.