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Role of human DNA g...
Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome.
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Mandal, Santi M (author)
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Hegde, Muralidhar L (author)
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Chatterjee, Arpita (author)
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Hegde, Pavana M (author)
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Szczesny, Bartosz (author)
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Banerjee, Dibyendu (author)
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Boldogh, Istvan (author)
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Gao, Rui (author)
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- Falkenberg, Maria, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Gustafsson, Claes M, 1966 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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Sarkar, Partha S (author)
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Hazra, Tapas K (author)
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(creator_code:org_t)
- 2012
- 2012
- English.
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In: The Journal of biological chemistry. - 1083-351X. ; 287:4, s. 2819-29
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Abstract
Subject headings
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- The repair of reactive oxygen species-induced base lesions and single strand breaks (SSBs) in the nuclear genome via the base excision (BER) and SSB repair (SSBR) pathways, respectively, is well characterize, and important for maintaining genomic integrity. However, the role of mitochondrial (mt) BER and SSBR proteins in mt genome maintenance is not completely clear. Here we show the presence of the oxidized base-specific DNA glycosylase Nei-like 2 (NEIL2) and the DNA end-processing enzyme polynucleotide kinase 3'-phosphatase (PNKP) in purified human mitochondrial extracts (MEs). Confocal microscopy revealed co-localization of PNKP and NEIL2 with the mitochondrion-specific protein cytochrome c oxidase subunit 2 (MT-CO2). Further, chromatin immunoprecipitation analysis showed association of NEIL2 and PNKP with the mitochondrial genes MT-CO2 and MT-CO3 (cytochrome c oxidase subunit 3); importantly, both enzymes also associated with the mitochondrion-specific DNA polymerase γ. In cell association of NEIL2 and PNKP with polymerase γ was further confirmed by proximity ligation assays. PNKP-depleted ME showed a significant decrease in both BER and SSBR activities, and PNKP was found to be the major 3'-phosphatase in human ME. Furthermore, individual depletion of NEIL2 and PNKP in human HEK293 cells caused increased levels of oxidized bases and SSBs in the mt genome, respectively. Taken together, these studies demonstrate the critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- Cytochromes c
- genetics
- metabolism
- DNA Breaks
- Single-Stranded
- DNA Glycosylases
- genetics
- metabolism
- DNA Repair
- physiology
- DNA Repair Enzymes
- genetics
- metabolism
- DNA-(Apurinic or Apyrimidinic Site) Lyase
- genetics
- metabolism
- DNA-Directed DNA Polymerase
- genetics
- metabolism
- Genome
- Mitochondrial
- physiology
- HEK293 Cells
- Humans
- Mitochondria
- enzymology
- genetics
- Mitochondrial Proteins
- genetics
- metabolism
- Phosphotransferases (Alcohol Group Acceptor)
- genetics
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mandal, Santi M
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Hegde, Muralidha ...
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Chatterjee, Arpi ...
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Hegde, Pavana M
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Szczesny, Bartos ...
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Banerjee, Dibyen ...
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show more...
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Boldogh, Istvan
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Gao, Rui
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Falkenberg, Mari ...
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Gustafsson, Clae ...
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Sarkar, Partha S
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Hazra, Tapas K
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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The Journal of b ...
- By the university
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University of Gothenburg