Mitochondrial base excision repair of uracil and AP sites takes place by single-nucleotide insertion and long-patch DNA synthesis

Akbari, Mansour; Visnes, Torkild; Krokan, Hans E.; Otterlei, Marit

doi:10.1016/j.dnarep.2008.01.002

Cited by 115 publications

(108 citation statements)

References 46 publications

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“…In most bacteria and yeast, this is the sole uracil-DNA glycosylase. UNG1 is also apparently the only uracil-DNA glycosylase in mitochondria, which was recently found to have capacity for both short-patch BER (insertion of one nucleotide) and long-patch BER (insertion of two to eight nucleotides) (Akbari et al 2008). All representatives of this family examined so far are active on both single-stranded and double-stranded DNA, but with a preference for uracil in single-stranded DNA.…”

Section: Mammalian Uracil-dna Glycosylases and Their Assumed Functionsmentioning

confidence: 99%

Uracil in DNA and its processing by different DNA glycosylases

Visnes

Doseth

Pettersen

et al. 2008

Phil. Trans. R. Soc. B

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108

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Uracil in DNA may result from incorporation of dUMP during replication and from spontaneous or enzymatic deamination of cytosine, resulting in U:A pairs or U:G mismatches, respectively. Uracil generated by activation-induced cytosine deaminase (AID) in B cells is a normal intermediate in adaptive immunity. Five mammalian uracil-DNA glycosylases have been identified; these are mitochondrial UNG1 and nuclear UNG2, both encoded by the UNG gene, and the nuclear proteins SMUG1, TDG and MBD4. Nuclear UNG2 is apparently the sole contributor to the post-replicative repair of U:A lesions and to the removal of uracil from U:G contexts in immunoglobulin genes as part of somatic hypermutation and class-switch recombination processes in adaptive immunity. All uracil-DNA glycosylases apparently contribute to U:G repair in other cells, but they are likely to have different relative significance in proliferating and non-proliferating cells, and in different phases of the cell cycle. There are also some indications that there may be species differences in the function of the uracil-DNA glycosylases.

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Section: Mammalian Uracil-dna Glycosylases and Their Assumed Functionsmentioning

confidence: 99%

Uracil in DNA and its processing by different DNA glycosylases

Visnes

Doseth

Pettersen

et al. 2008

Phil. Trans. R. Soc. B

Self Cite

108

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“…This flap is cleaved by a flap endonuclease, and the resulting nick is sealed by DNA ligase, completing the repair. Biochemical studies suggest that both short-patch and long-patch pathways are active in mitochondria (Akbari et al 2008;Liu et al 2008;Szczesny et al 2008). 1 In this study, we examine the mitochondrial roles of Apn1p, Ntg1p, and Ogg1p, three well-studied BER components.…”

Section: Epletion Of Mitochondrial Function Has Beenmentioning

confidence: 99%

Evidence That Msh1p Plays Multiple Roles in Mitochondrial Base Excision Repair

2009

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Mitochondrial DNA is thought to be especially prone to oxidative damage by reactive oxygen species generated through electron transport during cellular respiration. This damage is mitigated primarily by the base excision repair (BER) pathway, one of the few DNA repair pathways with confirmed activity on mitochondrial DNA. Through genetic epistasis analysis of the yeast Saccharomyces cerevisiae, we examined the genetic interaction between each of the BER proteins previously shown to localize to the mitochondria. In addition, we describe a series of genetic interactions between BER components and the MutS homolog MSH1, a respiration-essential gene. We show that, in addition to their variable effects on mitochondrial function, mutant msh1 alleles conferring partial function interact genetically at different points in mitochondrial BER. In addition to this separation of function, we also found that the role of Msh1p in BER is unlikely to be involved in the avoidance of large-scale deletions and rearrangements.

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“…MtDNA is partially associated with the inner mitochondrial membrane, where the respiratory complexes catalyze oxidative phosphorylation and generate high levels of ROS which causes mtDNA damage [14][15][16]. Oxidative mtDNA damage can be repaired by both short-patch BER and long-patch BER [17][18][19], and UNG1 is involved in the repair process [20][21][22]. In addition to mtDNA, proteins responsible for mtDNA BER may also be a target of the high level of ROS since they are associated with the inner mitochondrial membrane where the respiratory complexes reside [23].…”

Section: Introductionmentioning

confidence: 99%