Architecture of Y-Family DNA Polymerases Relevant to Translesion DNA Synthesis as Revealed in Structural and Molecular Modeling Studies
DNA adducts, which block replicative DNA polymerases (DNAPs), are often bypassed by lesion-bypass DNAPs, which are mostly in the Y-Family. Y-Family DNAPs can do non-mutagenic or mutagenic dNTP insertion, and understanding this difference is important, because mutations transform normal into tumorige...
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Published in | Journal of Nucleic Acids Vol. 2010; no. 2010; pp. 821 - 840 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
Cairo, Egypt
Hindawi Limiteds
01.01.2010
Hindawi Puplishing Corporation SAGE-Hindawi Access to Research Hindawi Limited |
Subjects | |
Online Access | Get full text |
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Summary: | DNA adducts, which block replicative DNA polymerases (DNAPs), are often bypassed by lesion-bypass DNAPs, which are mostly in the Y-Family. Y-Family DNAPs can do non-mutagenic or mutagenic dNTP insertion, and understanding this difference is important, because mutations transform normal into tumorigenic cells. Y-Family DNAP architecture that dictates mechanism, as revealed in structural and modeling studies, is considered. Steps from adduct blockage of replicative DNAPs, to bypass by a lesion-bypass DNAP, to resumption of synthesis by a replicative DNAP are described. Catalytic steps and protein conformational changes are considered. One adduct is analyzed in greater detail: the major benzo[a]pyrene adduct (B[a]P-N2-dG), which is bypassed non-mutagenically (dCTP insertion) by Y-family DNAPs in the IV/κ-class and mutagenically (dATP insertion) by V/η-class Y-Family DNAPs. Important architectural differences between IV/κ-class versus V/η-class DNAPs are discussed, including insights gained by analyzing ~400 sequences each for bacterial DNAPs IV and V, along with sequences from eukaryotic DNAPs kappa, eta and iota. The little finger domains of Y-Family DNAPs do not show sequence conservation; however, their structures are remarkably similar due to the presence of a core of hydrophobic amino acids, whose exact identity is less important than the hydrophobic amino acid spacing. |
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Bibliography: | Academic Editor: Ashis Basu |
ISSN: | 2090-021X 2090-0201 2090-021X |
DOI: | 10.4061/2010/784081 |