Sitio CpG: Diferenzas entre revisións
Contido eliminado Contido engadido
Liña 102:
[[Ficheiro:Demethylation of 5-methylcytosine.svg|miniatura|400 px|Desmetilación de [[5-metilcitosina]] (5mC) en ADN de neuronas. Como se revisou en 2018,<ref name="pmid29875631">{{cite journal |vauthors=Bayraktar G, Kreutz MR |title=The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders |journal=Front Mol Neurosci |volume=11 |issue= |pages=169 |date=2018 |pmid=29875631 |pmc=5975432 |doi=10.3389/fnmol.2018.00169 |url=}}</ref> en neuronas do cerebro, a 5mC é oxidado pola familia da translocación dez-once (TET) de dioxixenases ([[TET1]], [[TET2]], [[TET3]]) para xerar [[5-hidroximetilcitosina]] (5hmC). En pasos sucesivos os enzimas TET seguen hidolizando a 5hmC para xerar 5-formilcitosina (5fC) e 5-carboxilcitosina (5caC). A [[timina-ADN glicosilase]] (TDG) recoñece as bases intermedias 5fC e 5caC e escinde o [[enlace glicosídico]] resultante nun sitio apirimidínico ([[sitio AP]]). Nunha vía de [[desaminación oxidativa]] alternativa, a 5hmC pode ser desamimnada oxidativamente polas desaminases [[APOBEC3G|(AID/APOBEC)]] para formar 5-hidroximetiluracilo (5hmU) ou 5mC pode ser convertido en [[timina]] (Thy). O 5hmU pode ser clivado pola TDG, a [[SMUG1]], a [[NEIL1]], ou a [[MBD4]]. Os [[sitio AP|sitios AP]] e as discordancias T:G son despois reparadas por enzimas da [[reparación por escisión de bases]] (BER) para render [[citosina]] (Cyt).]]
<!--▼
Two reviews<ref name="pmid20649473">{{cite journal |vauthors=Massaad CA, Klann E |title=Reactive oxygen species in the regulation of synaptic plasticity and memory |journal=Antioxid. Redox Signal. |volume=14 |issue=10 |pages=2013–54 |date=May 2011 |pmid=20649473 |pmc=3078504 |doi=10.1089/ars.2010.3208 |url=}}</ref><ref name="pmid27625575">{{cite journal |vauthors=Beckhauser TF, Francis-Oliveira J, De Pasquale R |title=Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity |journal=J Exp Neurosci |volume=10 |issue=Suppl 1 |pages=23–48 |date=2016 |pmid=27625575 |pmc=5012454 |doi=10.4137/JEN.S39887 |url=}}</ref> summarize the large body of evidence for the critical and essential role of [[reactive oxygen species|ROS]] in [[memory]] formation. The [[DNA demethylation]] of thousands of CpG sites during memory formation depends on initiation by ROS. In 2016, Zhou et al.,<ref name=Zhou/> showed that ROS have a central role in [[DNA demethylation]].▼
▲
▲<!--
[[Tet methylcytosine dioxygenase 1|TET1]] is a key enzyme involved in demethylating 5mCpG. However, TET1 is only able to act on 5mCpG if an ROS has first acted on the guanine to form [[8-oxo-2'-deoxyguanosine|8-hydroxy-2'-deoxyguanosine]] (8-OHdG), resulting in a 5mCp-8-OHdG dinucleotide (see first figure in this section).<ref name=Zhou /> After formation of 5mCp-8-OHdG, the [[base excision repair]] enzyme [[oxoguanine glycosylase|OGG1]] binds to the 8-OHdG lesion without immediate excision. Adherence of OGG1 to the 5mCp-8-OHdG site recruits [[Tet methylcytosine dioxygenase 1|TET1]], allowing TET1 to oxidize the 5mC adjacent to 8-OHdG, as shown in the first figure in this section. This initiates the demethylation pathway shown in the second figure in this section.
| |||