Oxidation and deamination of nucleobases as an epigenetic tool
Journal Title: Advances in Hygiene and Experimental Medicine - Year 2012, Vol 66, Issue 0
Abstract
Recent discoveries have demonstrated that 5-methylcytosine (5mC) may be hydroxymethylated to 5-hydroxymethylcytosine (5hmC) in mammals and that genomic DNA may contain about 0.02–0.7% of 5hmC. The aforementioned modification is the key intermediate of active DNA demethylation and has been named “the sixth base in DNA”. Although active DNA demethylation in mammals is still controversial, the most plausible mechanism/s of active 5mC demethylation include involvement of three families of enzymes; i) Tet, which is involved in hydroxylation of 5mC to form 5hmC, which can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC); ii) deamination of 5mC (or 5hmC) by AID/APOBEC to form thymine or 5-hydroxymethyluracil (5hmU) mispaired with guanine; iii) the BER pathway induced by involvement of TDG glycosylase to replace the above described base modification (5fC, 5caC, 5hmU) with cytosine to demethylate DNA. A plausible scenario for engagement of TDG glycosylase (or some other G-T glycosylase) is through prior deamination of 5-mC to thymine, which generates a G: T substrate for the enzyme. Here cytidine deaminase of the AID/APOBEC family was implicated in the deamination step. It is possible that TDG may act in concert with these deaminases. It seems that mutations are not the only effect of oxidatively modified DNA bases. These, as yet, understudied aspects of the damage suggest a potential for 8-oxoguanine (8-oxoGua) to affect gene expression via chromatin relaxation. It is possible that 8-oxoGua presence in specific DNA sequences may be widely used for transcription regulation, which suggests the epigenetic nature of 8-oxoGua presence in DNA.
Authors and Affiliations
Jolanta Guz, Marek Jurgowiak, Ryszard Oliński
Diagnostic value of specifi c anty-HLA alloantibodies before and after renal transplantation. Programs for highly sensitized recipients
Anti-HLA alloantibodies are the main barrier in kidney transplantation. Lack of appropriate donors for highly sensitized (HS) recipients makes access to transplantation very diffi cult and results in a signifi cant incre...
Metformin – mechanisms of action and use for the treatment of type 2 diabetes mellitus
Metformin is widely used for the treatment of type 2 diabetes mellitus. Although this biguanide derivative has been used for more than 50 years, its mechanism of action has not been fully elucidated. In this article we...
Ocena wpływu stymulacji komórek mononuklearnych krwi obwodowej polisacharydami Streptococcus pneumoniae na ekspresję wybranych receptorów Toll-podobnych, markerów aktywacji oraz antygenu FAS u chorych na przewlekłą białaczkę limfocytową
Identification of circulating tumor cells as a promising method of genitourinary cancer diagnosis
Circulating tumor cells (CTCs) are cells circulating in the blood, which in terms of antigenic or genetic profile correspond to a particular type of cancer. It is suspected that CTCs possess properties of cancer stem cel...
Influence of different physical conditions on HIV infectivity
Dotąd nie udało się jeszcze określić jednoznacznie granicznych warunków fizycznych, w jakich HIV przestaje być zakaźny dla komórek ludzkich. Do utraty zdolności wirusa do zakażania nie jest konieczna jego całkowita ina...