التفاصيل البيبلوغرافية
| العنوان: |
Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function |
| المؤلفون: |
Michel, M., Benítez-Buelga, C., Calvo, P. A., Hanna, B. M. F., Mortusewicz, O., Masuyer, G., Davies, J., Wallner, O., Sanjiv, K., Albers, J. J., Castañeda-Zegarra, S., Jemth, A. -S, Visnes, T., Sastre-Perona, A., Danda, A. N., Homan, E. J., Marimuthu, K., Zhenjun, Z., Chi, C. N., Sarno, A., Wiita, E., von Nicolai, C., Komor, A. J., Rajagopal, V., Müller, S., Hank, E. C., Varga, M., Scaletti, E. R., Pandey, M., Karsten, S., Haslene-Hox, H., Loevenich, S., Marttila, P., Rasti, A., Mamonov, K., Ortis, F., Schömberg, F., Loseva, O., Stewart, J., D'Arcy-Evans, N., Koolmeister, T., Henriksson, M., Michel, Dana, de Ory, A., Acero, L., Calvete, O., Scobie, M., Hertweck, C., Vilotijevic, I., Kalderén, C., Osorio, A., Perona, R., Stolz, A., Stenmark, P., Berglund, U. W., de Vega, M., Helleday, T. |
| المصدر: |
Science. 376(6600):1471-1476 |
| مصطلحات موضوعية: |
8 oxoguanine DNA glycosylase 1, DNA glycosyltransferase, glycine, phenylalanine, polynucleotide kinase phosphatase 1, small molecule transport agent, th 1078, unclassified drug, DNA (apurinic or apyrimidinic site) lyase, activation energy, amino acid, catalysis, catalyst, cell, DNA, enzyme activity, nitrogen, phosphatase, aging, Article, controlled study, DNA repair, drug structure, enzyme active site, human, in vitro study, DNA damage, enzyme specificity, metabolism, oxidative stress, DNA Glycosylases, DNA-(Apurinic or Apyrimidinic Site) Lyase, Substrate Specificity |
| الوصف: |
Oxidative DNA damage is recognized by 8-oxoguanine (8-oxoG) DNA glycosylase 1 (OGG1), which excises 8-oxoG, leaving a substrate for apurinic endonuclease 1 (APE1) and initiating repair. Here, we describe a small molecule (TH10785) that interacts with the phenylalanine-319 and glycine-42 amino acids of OGG1, increases the enzyme activity 10-fold, and generates a previously undescribed b,d-lyase enzymatic function. TH10785 controls the catalytic activity mediated by a nitrogen base within its molecular structure. In cells, TH10785 increases OGG1 recruitment to and repair of oxidative DNA damage. This alters the repair process, which no longer requires APE1 but instead is dependent on polynucleotide kinase phosphatase (PNKP1) activity. The increased repair of oxidative DNA lesions with a small molecule may have therapeutic applications in various diseases and aging. © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works |
| وصف الملف: |
print |
| URL الوصول: |
https://urn.kb.se/resolve?urn=urn:nbn:se:ri:diva-59834 |
| قاعدة البيانات: |
SwePub |
