ISSN 1062-3604, Russian Journal of Developmental Biology, 2008, Vol. 38, No. 5, pp. 297–302. © Pleiades Publishing, Inc., 2008.
Original Russian Text © A.V. Makarova, L.V. Gening, I.V. Makarova, V.Z. Tarantul, 2008, published in Ontogenez, 2008, Vol. 38, No. 5, pp. 367–373.
In living organisms, DNA is constantly subject to
damage by various chemical and physical factors.
Sometimes, the repair systems have no time to repair
the damage before the next replication starts. However,
speciﬁc structure of the catalytic site in the processive
DNA polymerases that provide for exact replication of
genomic DNA does not allow them to synthesize on
damaged DNA regions. Nature has created DNA poly-
merases with a more open and template structure-toler-
ant catalytic site, which allows the synthesis on dam-
aged region, to relieve the replication block and to prevent
cell death. Such enzymes include prokaryotic Pol IV
) and Pol V (
) and eukaryotic Pol
, and REV1. Sometimes
these enzymes incorporate a correct nucleotide oppo-
site of the damage (error-free translesion DNA synthe-
sis), thus, restoring the original DNA structure. At the
same time, these DNA polymerases feature a high error
rate when undamaged DNA is used as a template,
which increases the error rate to
et al., 2000; Ohashi et al., 2000; Tissier et al., 2000;
Johnson et al., 2002a, 2002b). Accordingly, these
enzymes are called error-prone DNA polymerases.
DNA polymerase iota (Pol
) occupies a particular
place among error-prone DNA polymerases. Due to the
speciﬁc structure of the catalytic site and the use of
Hoogsteen rather than Watson–Crick’s pairing, human
exhibits a set of unusual properties. Pol
out some functions in genome stabilization. For
instance, human Pol
can remove the 5'dRP residue
remaining after AP endonuclease cleavage (dRP lyase
activity), which is necessary for the correct repair of
damaged DNA region during excision base repair
(Bebenek et al., 2001). Human Pol
can also incorpo-
rate guanine opposite uracil, which allows the cell to
prevent transitions caused by cytosine deamination
(Vaisman and Woodgate, 2001; Vaisman et al., 2006).
Finally, this enzyme is able to carry out synthesis opposite
a variety of DNA damages (AP-sites, various purine
adducts, etc.) with different efﬁciency and ﬁdelity.
At the same time, human Pol
has the lowest ﬁdelity
of undamaged DNA synthesis among all DNA poly-
merases known to date (McDonald et al., 2001). In this
case, new nucleotides are incorporated opposite four
DNA bases with different accuracy and efﬁciency. The
enzyme incorporates dGTP opposite thymidine (by the
mechanism used for incorporation opposite uracil) sev-
eral times more efﬁciently than canonical dATP (Zhang
et al., 2000). Pol
carries out more accurate and efﬁ-
cient synthesis opposite purines than opposite pyrim-
idines (Johnson et al., 2000a; Tissier et al., 2000; Zhang
et al., 2000; Washington et al., 2004).
The expression of many genes is tissue speciﬁc, and
the expression proﬁle considerably varies during
mRNA is detected in all human tissues
although at different levels: the highest level was
observed in the testicles, and its level in the heart and
pancreas was also considerable. In adult mouse, the
highest level of Pol
mRNA was also observed in the
testicles, while insigniﬁcant expression level was
detected in the lung, brain, and spleen (McDonald et al.,
mRNA was isolated from the testicles
(BC121199) and gastrula cells (DQ102380) of
however, no serious attempts to evaluate this
enzyme expression during ontogeny have been made.
It is common knowledge that enzyme activity is a
more complete description of its expression than
mRNA quantitation in cells. Previously, we proposed to
test biochemical activity of Pol
in crude extracts from
different tissues and organs of animals based on the
Activity of Error-Prone DNA Polymerase Iota in Different
Periods of House Mouse
A. V. Makarova, L. V. Gening, I. V. Makarova, and V. Z. Tarantul
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow 123182, Russia
Received February 4, 2008; in ﬁnal form, February 14, 2008.
—Analysis of incorrect activity of error-prone DNA polymerase iota in
onstrated considerable changes in its activity, which peaks in most organs during prenatal development and
decreases in the adult body. We propose that the capacity of error-prone DNA polymerases to synthesize on
damaged DNA regions is critical for the realization of rapidly changing genetic program in mammalian
embryogenesis, which relieves the replication block and prevents cell death.
: DNA polymerase iota, incorrect activity, DNA damage, hypermutagenesis.