Document Type
Article
Date of Original Version
6-21-2016
Department
Biomedical and Pharmaceutical Sciences
Abstract
XPC-RAD23B (XPC) plays a critical role in human nucleotide excision repair (hNER) as this complex recognizes DNA adducts to initiate NER. To determine the mutagenic potential of structurally different bulky DNA damages, various studies have been conducted to define the correlation of XPC-DNA damage equilibrium binding affinity with NER efficiency. However, little is known about the effects of XPC-DNA damage recognition kinetics on hNER. Although association of XPC is important, our current work shows that the XPC-DNA dissociation rate also plays a pivotal role in achieving NER efficiency.We characterized for the first time the binding of XPC to mono- versus di-AAF-modified sequences by using the real time monitoring surface plasmon resonance technique. Strikingly, the half-life (t1/2 or the retention time of XPC in association with damaged DNA) shares an inverse relationship with NER efficiency. This is particularly true when XPC remained bound to clustered adducts for a much longer period of time as compared to mono-adducts. Our results suggest that XPC dissociation from the damage site could become a rate-limiting step in NER of certain types of DNA adducts, leading to repression of NER.
Citation/Publisher Attribution
Hilton B, Gopal S, Xu L, Mazumder S, Musich PR, et al. (2016) Dissociation Dynamics of XPC-RAD23B from Damaged DNA Is a Determining Factor of NER Efficiency. PLOS ONE 11(6): e0157784. https://doi.org/10.1371/journal.pone.0157784
Available at: https://doi.org/10.1371/journal.pone.0157784
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.