The Hyperthermophilic Euryarchaeon Archaeoglobus fulgidus Repairs Uracil by Single-Nucleotide Replacement
2010
Hydrolytic
deaminationof cytosine to
uracilin cellular DNA is a major source of C-to-T transition mutations if
uracilis not repaired by the DNA
base excision repair(BER) pathway. Since
deaminationincreases rapidly with temperature,
hyperthermophiles, in particular, are expected to succumb to such damage. There has been only one report of crenarchaeotic BER showing strong similarities to that in most eukaryotes and bacteria for
hyperthermophilic
Archaea. Here we report a different type of BER performed by extract prepared from cells of the euryarchaeon
Archaeoglobus fulgidus. Although immunodepletion showed that the monofunctional family 4 type of
uracil-DNA glycosylase(UDG) is the principal and probably only UDG in this organism, a β-elimination mechanism rather than a hydrolytic mechanism is employed for incision of the abasic site following
uracilremoval. The resulting 3' remnant is removed by efficient 3'-phosphodiesterase activity followed by single-nucleotide insertion and ligation. The finding that repair product formation is stimulated similarly by ATP and ADP in vitro raises the question of whether ADP is more important in vivo because of its higher
heat stability.
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