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- Wollen Steen, Kristian, et al.
(författare)
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MtSSB may sequester UNG1 at mitochondrial ssDNA and delay uracil processing until the dsDNA conformation is restored
- 2012
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7864 .- 1568-7856. ; 11:1, s. 82-91
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Tidskriftsartikel (refereegranskat)abstract
- Single-strand DNA binding proteins protect DNA from nucleolytic damage, prevent formation of secondary structures and prevent premature reannealing of DNA in DNA metabolic transactions. In eukaryotes, the nuclear single-strand DNA binding protein RPA is essential for chromosomal DNA replication and transcription and directly participates in several DNA repair processes by binding to and modulating the activity of repair factors. Much less is known about the involvement of the only mitochondrial single-strand binding protein mtSSB in the context of DNA repair. Here we demonstrate that mtSSB impedes excision of uracil and oxidative demethylation of 3meC in single-stranded DNA by UNG1 and ABH1, respectively, whereas excision by NEIL1 was partially inhibited. mtSSB also effectively inhibited nicking of single-stranded DNA by APE1 and ABH1 and partially inhibited the lyase activity of NEIL1. Finally we identified a putative surface motif in mtSSB that may recruit UNG1 to DNA-bound mtSSB. We suggest that the massive amount of mtSSB in mitochondria effectively prevents processing of uracil and other types of damaged bases to avoid introduction of nicks in single-stranded mtDNA formed during replication. Local enrichment of UNG1 at DNA-bound mtSSB may furthermore facilitate rapid access to- and processing of the damage once the dsDNA conformation is restored. This could be of potential biological importance, since mitochondria have no or limited capacity for homologous recombination to process nicks at the replication fork. © 2011 Elsevier B.V.
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| 2. |
- Uhler, Jay (Jennifer), et al.
(författare)
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Primer removal during mammalian mitochondrial DNA replication
- 2015
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7864. ; 34, s. 28-38
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Forskningsöversikt (refereegranskat)abstract
- The small circular mitochondrial genome in mammalian cells is replicated by a dedicated replisome, defects in which can cause mitochondrial disease in humans. A fundamental step in mitochondrial DNA (mtDNA) replication and maintenance is the removal of the RNA primers needed for replication initiation. The nucleases RNase H1, PEN1, DNA2, and MGME1 have been implicated in this process. Here we review the role of these nucleases in the light of primer removal pathways in mitochondria, highlight associations with disease, as well as consider the implications for mtDNA replication initiation. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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