Understanding the role of ADP-ribosylation in regulating DNA repair

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The human genome is under frequent attack from a number of exogenous and endogenous sources of DNA damage which can threaten genome integrity and cause genome instability. In order to mitigate the negative effects of DNA damage, human cells have evolved a range of protective mechanisms to resolve DNA lesions. Collectively, these pathways are known as the DNA damage response (DDR). Poly (ADP-ribose) polymerases (PARPs) are a superfamily of 17 proteins with a variety of cellular functions, and PARP1 and 2 are known to play important roles in single strand break repair (SSBR). However, the roles of additional PARPs in this pathway are relatively ill-defined. PARP inhibitors (PARPi) are used in the clinic to treat patients with chemo-resistant ovarian cancer, but their clinical efficacy may be reduced by not targeting all of the PARPs involved in SSBR. By further exploring the functional roles of PARPs in the DDR, we aim to pave the way for the development of novel PARP inhibitors that target specific PARPs and have greater clinical efficacy. This proposed research addresses the healthy ageing across lifecourse BBSRC priority area and aligns with the Bisocience for Health DTP priority area. BfH, WCUB, ENWW