FKBP52 and its role in DNA damage repair

This thesis aimed to determine if FKBP52 had a role in the DNA Damage repair pathways and what that role may be. FKBP52 was found to co-localise with known DNA damage protein hSSB1. FKBP52 expression responded to IR induced DNA damage. FKBP52 levels were also found to increase in the nucleus in response to IR and was found to be bound to the nucleus, this suggests it was involved in the DNA damage response. FKBP52 depletion also led to altered DNA damage signalling in particular with the phosphorylation of key regulatory proteins of the DNA damage pathway. It was also found that reduced levels via siRNA led to reduced survival after IR via clonogenic assays and reduced the efficiency of HR via the HR assay. FKBP52 levels in the nucleus were shown to be regulated by ATM and ATR consistent with this FKBP52 was found to be phosphorylated following IR on a putative ATM/ATR phosphorylation site. It was found that phosphorylation at this site lead to altered expression of the FKBP52 protein.