Abstract
DNA lesion bypass is an important cellular response to genomic damage during replication. Human DNA polymerase η (Polη), encoded by the
Xeroderma pigmentosum variant
(
XPV
) gene, is known for its activity of error-free translesion synthesis opposite a TT
cis
-
syn
cyclobutane dimer. Using purified human Polη, we have examined bypass activities of this polymerase opposite several other DNA lesions. Human Polη efficiently bypassed a template 8-oxoguanine, incorporating an A or a C opposite the lesion with similar efficiencies. Human Polη effectively bypassed a template abasic site, incorporating an A and less frequently a G opposite the lesion. Significant –1 deletion was also observed when the template base 5′ to the abasic site is a T. Human Polη partially bypassed a template (+)-
trans
-
anti
-benzo[
a
]pyrene-
N
2
-dG and predominantly incorporated an A, less frequently a T, and least frequently a G or a C opposite the lesion. This specificity of nucleotide incorporation correlates well with the known mutation spectrum of (+)-
trans
-
anti
-benzo[a]pyrene-
N
2
-dG lesion in mammalian cells. These results show that human Polη is capable of error-prone translesion DNA syntheses
in vitro
and suggest that Polη may bypass certain lesions with a mutagenic consequence in humans.
