Date of Award
Doctor of Philosophy in Biological and Environmental Sciences
Cell and Molecular Biology (CMB)
Cell & Molecular Biology
Fanconi Anemia (FA) is a rare autosomal and X-linked disease characterized by multiple congenital abnormalities, progressive bone marrow failure, and cancer predisposition. FA is caused by a biallelic mutation of any one of 21 genes; the proteins encoded by these genes regulate the removal of DNA interstrand crosslinks (ICLs) and are essential for maintaining chromosomal stability. This pathway is tightly regulated by posttranslational modifications (PTMs) such as ubiquitination and phosphorylation. Several kinases such as ATM, ATR and PLK1 have been linked to the pathway but no phosphatase has been firmly linked to the pathway. PTEN is a duel specificity phosphatase, capable of removing phosphate groups from phosphorylated lipids and also phosphorylated serine, threonine, and tyrosine residues, and it has recently been connected to genome stability. The goal of this research was to determine mechanistically PTEN’s role in DNA repair. Through this research, we have established that PTEN is necessary for a functional FA pathway, and this is dependent on its protein phosphatase activity and its ability to be SUMOylated on residue K254.
Vuono, Elizabeth Ann, "Characterization of the Role of the Phosphatase and Tensin Homolog, PTEN, in DNA Crosslink Repair" (2016). Open Access Dissertations. Paper 534.