title: Lesion bypass activities of human DNA polymerase mu.
abstract: DNA polymerase mu (Polmu) is a newly discovered member of the polymerase X family with unknown cellular function. The understanding of Polmu function should be facilitated by an understanding of its biochemical activities. By using purified human Polmu for biochemical analyses, we discovered the lesion bypass activities of this polymerase in response to several types of DNA damage. When it encountered a template 8-oxoguanine, abasic site, or 1,N(6)-ethenoadenine, purified human Polmu efficiently bypassed the lesion. Even bulky DNA adducts such as N-2-acetylaminofluorene-adducted guanine, (+)- and (-)-trans-anti-benzo[a]pyrene-N(2)-dG were unable to block the polymerase activity of human Polmu. Bypass of these simple base damage and bulky adducts was predominantly achieved by human Polmu through a deletion mechanism. The Polmu specificity of nucleotide incorporation indicates that the deletion resulted from primer realignment before translesion synthesis. Purified human Polmu also effectively bypassed a template cis-syn TT dimer. However, this bypass was achieved in a mainly error-free manner with AA incorporation opposite the TT dimer. These results provide new insights into the biochemistry of human Polmu and show that efficient translesion synthesis activity is not strictly confined to the Y family polymerases.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington 40536, USA.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
authors.forename: Dongyu
authors.initials: D
authors.lastname: Guo
authors.forename: Olga
authors.initials: O
authors.lastname: Rechkoblit
authors.forename: John-Stephen
authors.initials: JS
authors.lastname: Taylor
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Geacintov
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D018736:DNA Adducts; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism* / Q000502:physiology*; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D014466:Ultraviolet Rays
chemical_list: D018736:DNA Adducts; C407743:DNA polymerase mu; D004259:DNA-Directed DNA Polymerase