TY - JOUR
T1 - Lesion bypass activities of human DNA polymerase μ
AU - Zhang, Yanbin
AU - Wu, Xiaohua
AU - Guo, Dongyu
AU - Rechkoblit, Olga
AU - Taylor, John Stephen
AU - Geacintov, Nicholas E.
AU - Wang, Zhigang
PY - 2002/11/15
Y1 - 2002/11/15
N2 - DNA polymerase μ (Polμ) is a newly discovered member of the polymerase X family with unknown cellular function. The understanding of Polμ function should be facilitated by an understanding of its biochemical activities. By using purified human Polμ 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,N6-ethenoadenine, purified human Polμ efficiently bypassed the lesion. Even bulky DNA adducts such as N-2-acetylaminofluorene-adducted guanine, (+)-and (-)-trans-anti-benzo[a]pyrene-N2-dG were unable to block the polymerase activity of human Polμ. Bypass of these simple base damage and bulky adducts was predominantly achieved by human Polμ through a deletion mechanism. The Polμ specificity of nucleotide incorporation indicates that the deletion resulted from primer realignment before translesion synthesis. Purified human Polμ 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 Polμ and show that efficient translesion synthesis activity is not strictly confined to the Y family polymerases.
AB - DNA polymerase μ (Polμ) is a newly discovered member of the polymerase X family with unknown cellular function. The understanding of Polμ function should be facilitated by an understanding of its biochemical activities. By using purified human Polμ 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,N6-ethenoadenine, purified human Polμ efficiently bypassed the lesion. Even bulky DNA adducts such as N-2-acetylaminofluorene-adducted guanine, (+)-and (-)-trans-anti-benzo[a]pyrene-N2-dG were unable to block the polymerase activity of human Polμ. Bypass of these simple base damage and bulky adducts was predominantly achieved by human Polμ through a deletion mechanism. The Polμ specificity of nucleotide incorporation indicates that the deletion resulted from primer realignment before translesion synthesis. Purified human Polμ 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 Polμ and show that efficient translesion synthesis activity is not strictly confined to the Y family polymerases.
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U2 - 10.1074/jbc.M207297200
DO - 10.1074/jbc.M207297200
M3 - Article
C2 - 12228225
AN - SCOPUS:0037113885
SN - 0021-9258
VL - 277
SP - 44582
EP - 44587
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -