Oxidative lesions are removed from DNA primarily via the base excision repair (BER) pathway. BER is carried out through four enzymatic steps, but it is now clear that several other proteins modulate BER efficiency through protein-protein interactions. We and others identified several protein interactions for the core BER enzymes. These protein interactions are physical and functional and together support the """"""""passing of baton"""""""" model, in which BER takes place in different steps supported by individual protein interactions that are components of a repair complex, possibly situated at the DNA lesion. We are studying other protein interactions of OGG1 in order to understand how repair of oxidative lesions is regulated in vivo. We find that OGG1 also interacts with the recombination protein RAD52, suggesting a possible interplay between these two repair pathways. We find a reciprocal functional interaction between these two proteins, in which RAD52 stimulates OGG1 catalytic activity and OGG1 inhibits RAD52-catalysed DNA strand annealing and invasion. Moreover, the physical interaction between OGG1 and RAD52 increases in cells exposed to oxidative stress, indicating that this interaction is important in the cellular response to oxidative DNA damage. Since stem cells are critically important in development, it is very important to understand how these cells maintain their genome. We have therefore examined DNA repair properties in human embryonic stem cells. Interestingly, these cells have upregulated DNA repair and one of the pathways that is markedly upregulated is the base excision repair pathway for removal of oxidative DNA damage. This testifies to the central importance of this pathway in development.
| Fang, Evandro Fei; Froetscher, Lynn; Scheibye-Knudsen, Morten et al. (2018) Emerging antitumor activities of the bitter melon (Momordica charantia). Curr Protein Pept Sci : |
| Baptiste, Beverly A; Katchur, Steven R; Fivenson, Elayne M et al. (2018) Enhanced mitochondrial DNA repair of the common disease-associated variant, Ser326Cys, of hOGG1 through small molecule intervention. Free Radic Biol Med 124:149-162 |
| Rahnasto-Rilla, Minna K; McLoughlin, Padraig; Kulikowicz, Tomasz et al. (2017) The Identification of a SIRT6 Activator from Brown Algae Fucus distichus. Mar Drugs 15: |
| Fang, Evandro F; Bohr, Vilhelm A (2017) NAD(+): The convergence of DNA repair and mitophagy. Autophagy 13:442-443 |
| Fakouri, Nima Borhan; Durhuus, Jon Ambæk; Regnell, Christine Elisabeth et al. (2017) Rev1 contributes to proper mitochondrial function via the PARP-NAD+-SIRT1-PGC1? axis. Sci Rep 7:12480 |
| Hou, Yujun; Song, Hyundong; Croteau, Deborah L et al. (2017) Genome instability in Alzheimer disease. Mech Ageing Dev 161:83-94 |
| Karikkineth, Ajoy C; Scheibye-Knudsen, Morten; Fivenson, Elayne et al. (2017) Cockayne syndrome: Clinical features, model systems and pathways. Ageing Res Rev 33:3-17 |
| Fang, Evandro Fei; Scheibye-Knudsen, Morten; Chua, Katrin F et al. (2016) Nuclear DNA damage signalling to mitochondria in ageing. Nat Rev Mol Cell Biol 17:308-21 |
| Mitchell, Sarah J; Madrigal-Matute, Julio; Scheibye-Knudsen, Morten et al. (2016) Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metab 23:1093-1112 |
| Van Meter, Michael; Simon, Matthew; Tombline, Gregory et al. (2016) JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks. Cell Rep 16:2641-2650 |
Showing the most recent 10 out of 78 publications
