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- Lagunas-Rangel, Francisco Alejandro
(författare)
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Current role of mammalian sirtuins in DNA repair
- 2019
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Ingår i: DNA Repair. - : Elsevier BV. - 1568-7864 .- 1568-7856. ; 80:2508, s. 85-92
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Forskningsöversikt (refereegranskat)abstract
- Cellular DNA is constantly challenged by damage-inducing factors derived from exogenous or endogenous sources. Thus, to protect against DNA damage, cells have evolved complex and finely regulated mechanisms collectively known as DNA-damage response (DDR). However, DNA repair in eukaryotes does not occur merely in naked DNA but also within a highly organized and compacted chromatin environment, which ultimately participates in regulating DDR pathways. Thus, remodelling of the chromatin surrounding areas containing damaged DNA is required to allow access to the DNA repair machinery, as well as post-translational modifications in many repair factors to recruit and activate them at the damaged site. Notably, proteins such as sirtuins, which are NAD+-dependent deacetylases, have evolved to modulate multiple repair pathways through deacetylation of some repair factors, influencing chromatin accessibility or indirectly modulating cell cycle and preventing oxidative stress. In this way, the purpose of this review is to summarize the recent knowledge that links sirtuins with DNA repair, with a particular emphasis on the molecular mechanisms associated with coordination and regulation of this vital process.
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| 3. |
- 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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