We have previously demonstrated that the two
Exonuclease III (Xth) family members present
within the obligate human pathogen Neisseria
meningitidis, NApe and NExo, are important for
survival under conditions of oxidative stress. Of
these, only NApe possesses AP endonuclease
activity, while the primary function of NExo
remained unclear. We now reveal further functional
specialization at the level of 30
-PO4 processing for
NExo. We demonstrate that the bi-functional meningococcal
glycosylases Nth and MutM can perform
strand incisions at abasic sites in addition to NApe.
However, no such functional redundancy exists
for the 30
-phosphatase activity of NExo, and the
cytotoxicity of 30
-blocking lesions is reflected
in the marked sensitivity of a mutant lacking
NExo to oxidative stress, compared to strains
deficient in other base excision repair enzymes. A
histidine residue within NExo that is responsible
for its lack of AP endonuclease activity is
also important for its 30
-phosphatase activity,
demonstrating an evolutionary trade off in enzyme
function at the single amino acid level. This specialization
of two Xth enzymes for the 30
-end processing
and strand-incision reactions has not
previously been observed and provides a new
paradigm within the prokaryotic world for separation
of these critical functions during base
excision repair.