An overview of Y-Family DNA polymerases and a case study of human DNA polymerase η.
Y-Family DNA polymerases specialize in translesion synthesis, bypassing damaged bases that would otherwise block the normal progression of replication forks. Y-Family polymerases have unique structural features that allow them to bind damaged DNA and use a modified template base to direct nucleotide incorporation. Each Y-Family polymerase is unique and has different preferences for lesions to bypass and for dNTPs to incorporate. Y-Family polymerases are also characterized by a low catalytic efficiency, a low processivity, and a low fidelity on normal DNA. Recruitment of these specialized polymerases to replication forks is therefore regulated. The catalytic center of the Y-Family polymerases is highly conserved and homologous to that of high-fidelity and high-processivity DNA replicases. In this review, structural differences between Y-Family and A- and B-Family polymerases are compared and correlated with their functional differences. A time-resolved X-ray crystallographic study of the DNA synthesis reaction catalyzed by the Y-Family DNA polymerase human polymerase η revealed transient elements that led to the nucleotidyl-transfer reaction.
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892, United States.
Wei
W
Yang
D018360:Crystallography, X-Ray; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry* / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D013379:Substrate Specificity; D014466:Ultraviolet Rays; D000099270:Y-Family DNA Polymerases
D004247:DNA; D004259:DNA-Directed DNA Polymerase; D003854:Deoxyribonucleotides; D008274:Magnesium; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases