architecture of y-family dna polymerases relevant to translesion dna synthesis as revealed in structural and molecular modeling studies架构的大家庭的dna聚合酶与dna合成translesion透露在结构和分子建模研究.pdfVIP

SAGE-Hindawi Access to Research Journal of Nucleic Acids Volume 2010, Article ID 784081, 20 pages doi:10.4061/2010/784081 Review Article Architecture of Y-Family DNA Polymerases Relevant to Translesion DNA Synthesis as Revealed in Structural and Molecular Modeling Studies Sushil Chandani,1 Christopher Jacobs,2 and Edward L. Loechler1 1 Biology Department, Boston University, Boston, MA 02215, USA 2 Graduate Program in Bioinformatics, Boston University, Boston, MA 02215, USA Correspondence should be addressed to Edward L. Loechler, loechler@ Received 6 July 2010; Accepted 26 July 2010 Academic Editor: Ashis Basu Copyright © 2010 Sushil Chandani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 archite