Compromised incision of oxidized pyrimidines in liver mitochondria of mice deficient in NTH1 and OGG1 glycosylases - PubMed (original) (raw)
. 2003 Sep 5;278(36):33701-7.
doi: 10.1074/jbc.M301617200. Epub 2003 Jun 22.
Affiliations
- PMID: 12819227
- DOI: 10.1074/jbc.M301617200
Free article
Compromised incision of oxidized pyrimidines in liver mitochondria of mice deficient in NTH1 and OGG1 glycosylases
Bensu Karahalil et al. J Biol Chem. 2003.
Free article
Abstract
Mitochondrial DNA is constantly exposed to high levels of endogenously produced reactive oxygen species, resulting in elevated levels of oxidative damaged DNA bases. A large spectrum of DNA base alterations can be detected after oxidative stress, and many of these are highly mutagenic. Thus, an efficient repair of these is necessary for survival. Some of the DNA repair pathways involved have been characterized, but others are not yet determined. A DNA repair activity for thymine glycol and other oxidized pyrimidines has been described in mammalian mitochondria, but the nature of the glycosylases involved in this pathway remains unclear. The generation of mouse strains lacking murine thymine glycol-DNA glycosylase (mNTH1) and/or murine 8-oxoguanine-DNA glycosylase (mOGG1), the two major DNA N-glycosylase/apurinic/apyrimidinic (AP) lyases involved in the repair of oxidative base damage in the nucleus, has provided very useful biological model systems for the study of the function of these and other glycosylases in mitochondrial DNA repair. In this study, mouse liver mitochondrial extracts were generated from mNTH1-, mOGG1-, and [mNTH1, mOGG1]-deficient mice to ascertain the role of each of these glycosylases in the repair of oxidized pyrimidine base damage. We also characterized for the first time the incision of various modified bases in mitochondrial extracts from a double-knock-out [mNTH1, mOGG1]-deficient mouse. We show that mNTH1 is responsible for the repair of thymine glycols in mitochondrial DNA, whereas other glycosylase/AP lyases also participate in removing other oxidized pyrimidines, such as 5-hydroxycytosine and 5-hydroxyuracil. We did not detect a backup glycosylase or glycosylase/AP lyase activity for thymine glycol in the mitochondrial mouse extracts.
Similar articles
- Repair of dihydrouracil supported by base excision repair in mNTH1 knock-out cell extracts.
Elder RH, Dianov GL. Elder RH, et al. J Biol Chem. 2002 Dec 27;277(52):50487-90. doi: 10.1074/jbc.M208153200. Epub 2002 Oct 24. J Biol Chem. 2002. PMID: 12401779 - A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue.
Takao M, Kanno S, Kobayashi K, Zhang QM, Yonei S, van der Horst GT, Yasui A. Takao M, et al. J Biol Chem. 2002 Nov 1;277(44):42205-13. doi: 10.1074/jbc.M206884200. Epub 2002 Aug 27. J Biol Chem. 2002. PMID: 12200441 - Novel nuclear and mitochondrial glycosylases revealed by disruption of the mouse Nth1 gene encoding an endonuclease III homolog for repair of thymine glycols.
Takao M, Kanno S, Shiromoto T, Hasegawa R, Ide H, Ikeda S, Sarker AH, Seki S, Xing JZ, Le XC, Weinfeld M, Kobayashi K, Miyazaki J, Muijtjens M, Hoeijmakers JH, van der Horst G, Yasui A. Takao M, et al. EMBO J. 2002 Jul 1;21(13):3486-93. doi: 10.1093/emboj/cdf350. EMBO J. 2002. PMID: 12093749 Free PMC article. - Multiple DNA glycosylases for repair of 8-oxoguanine and their potential in vivo functions.
Hazra TK, Hill JW, Izumi T, Mitra S. Hazra TK, et al. Prog Nucleic Acid Res Mol Biol. 2001;68:193-205. doi: 10.1016/s0079-6603(01)68100-5. Prog Nucleic Acid Res Mol Biol. 2001. PMID: 11554297 Review. - Properties and functions of human uracil-DNA glycosylase from the UNG gene.
Krokan HE, Otterlei M, Nilsen H, Kavli B, Skorpen F, Andersen S, Skjelbred C, Akbari M, Aas PA, Slupphaug G. Krokan HE, et al. Prog Nucleic Acid Res Mol Biol. 2001;68:365-86. doi: 10.1016/s0079-6603(01)68112-1. Prog Nucleic Acid Res Mol Biol. 2001. PMID: 11554311 Review.
Cited by
- Expression and the Peculiar Enzymatic Behavior of the Trypanosoma cruzi NTH1 DNA Glycosylase.
Ormeño F, Barrientos C, Ramirez S, Ponce I, Valenzuela L, Sepúlveda S, Bitar M, Kemmerling U, Machado CR, Cabrera G, Galanti N. Ormeño F, et al. PLoS One. 2016 Jun 10;11(6):e0157270. doi: 10.1371/journal.pone.0157270. eCollection 2016. PLoS One. 2016. PMID: 27284968 Free PMC article. - Mitochondrial DNA alterations and reduced mitochondrial function in aging.
Hebert SL, Lanza IR, Nair KS. Hebert SL, et al. Mech Ageing Dev. 2010 Jul-Aug;131(7-8):451-62. doi: 10.1016/j.mad.2010.03.007. Epub 2010 Mar 20. Mech Ageing Dev. 2010. PMID: 20307565 Free PMC article. Review. - Mitochondrial DNA maintenance: an appraisal.
Akhmedov AT, Marín-García J. Akhmedov AT, et al. Mol Cell Biochem. 2015 Nov;409(1-2):283-305. doi: 10.1007/s11010-015-2532-x. Epub 2015 Aug 19. Mol Cell Biochem. 2015. PMID: 26286847 Review. - Mitochondrial determinants of cancer health disparities.
Choudhury AR, Singh KK. Choudhury AR, et al. Semin Cancer Biol. 2017 Dec;47:125-146. doi: 10.1016/j.semcancer.2017.05.001. Epub 2017 May 6. Semin Cancer Biol. 2017. PMID: 28487205 Free PMC article. Review. - Interleukin-6 is an important mediator for mitochondrial DNA repair after alcoholic liver injury in mice.
Zhang X, Tachibana S, Wang H, Hisada M, Williams GM, Gao B, Sun Z. Zhang X, et al. Hepatology. 2010 Dec;52(6):2137-47. doi: 10.1002/hep.23909. Epub 2010 Oct 7. Hepatology. 2010. PMID: 20931558 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials