Molecular Mechanisms Of DNA Repair Inhibition By Caffeine

paymanz

Member
Joined
Jan 6, 2015
Messages
2,707
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC53933/


Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA.
 
OP
P

paymanz

Member
Joined
Jan 6, 2015
Messages
2,707
Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells.

http://www.ncbi.nlm.nih.gov/pubmed/7767978

We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.
 
Joined
Nov 26, 2013
Messages
7,370
Interesting, perhaps that is the role of sleep?
 
Joined
Nov 26, 2013
Messages
7,370
paymanz1 said:
Such_Saturation said:
Interesting, perhaps that is the role of sleep?
why sleep?

Well caffeine looks like adenosine, does it not? It also looks like some of these things involved in photolyase which perhaps are themselves important for circadian clocks. And people always say that sleep repairs DNA.
 
OP
P

paymanz

Member
Joined
Jan 6, 2015
Messages
2,707
Such_Saturation said:
paymanz1 said:
Such_Saturation said:
Interesting, perhaps that is the role of sleep?
why sleep?

Well caffeine looks like adenosine, does it not? It also looks like some of these things involved in photolyase which perhaps are themselves important for circadian clocks. And people always say that sleep repairs DNA.
because caffeine disturbs sleep?!
maybe
 
Joined
Nov 26, 2013
Messages
7,370
Well yes, they say it is a "adenosine "receptor" antagonist".
 
Back
Top Bottom