TY - JOUR
T1 - Structural Basis for Error-free Replication of Oxidatively Damaged DNA by Yeast DNA Polymerase η
AU - Silverstein, Timothy D.
AU - Jain, Rinku
AU - Johnson, Robert E.
AU - Prakash, Louise
AU - Prakash, Satya
AU - Aggarwal, Aneel K.
N1 - Funding Information:
We thank the staff at Brookhaven National Laboratory (X29) and the Advanced Photon Source (24ID) for facilitating X-ray data collection. We thank D.T. Nair, S. Lone, R. Vasquez-Del Carpio, and M. Swan for help and discussions. This study was supported by NIH grants ES017767 and CA107650.
PY - 2010/11/10
Y1 - 2010/11/10
N2 - 7,8-dihydro-8-oxoguanine (8-oxoG) adducts are formed frequently by the attack of oxygen-free radicals on DNA. They are among the most mutagenic lesions in cells because of their dual coding potential, where, in addition to normal base-pairing of 8-oxoG(anti) with dCTP, 8-oxoG in the syn conformation can base pair with dATP, causing G to T transversions. We provide here for the first time a structural basis for the error-free replication of 8-oxoG lesions by yeast DNA polymerase η (Polη). We show that the open active site cleft of Polη can accommodate an 8-oxoG lesion in the anti conformation with only minimal changes to the polymerase and the bound DNA: at both the insertion and post-insertion steps of lesion bypass. Importantly, the active site geometry remains the same as in the undamaged complex and provides a basis for the ability of Polη to prevent the mutagenic replication of 8-oxoG lesions in cells.
AB - 7,8-dihydro-8-oxoguanine (8-oxoG) adducts are formed frequently by the attack of oxygen-free radicals on DNA. They are among the most mutagenic lesions in cells because of their dual coding potential, where, in addition to normal base-pairing of 8-oxoG(anti) with dCTP, 8-oxoG in the syn conformation can base pair with dATP, causing G to T transversions. We provide here for the first time a structural basis for the error-free replication of 8-oxoG lesions by yeast DNA polymerase η (Polη). We show that the open active site cleft of Polη can accommodate an 8-oxoG lesion in the anti conformation with only minimal changes to the polymerase and the bound DNA: at both the insertion and post-insertion steps of lesion bypass. Importantly, the active site geometry remains the same as in the undamaged complex and provides a basis for the ability of Polη to prevent the mutagenic replication of 8-oxoG lesions in cells.
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U2 - 10.1016/j.str.2010.08.019
DO - 10.1016/j.str.2010.08.019
M3 - Article
C2 - 21070945
AN - SCOPUS:78149443814
SN - 0969-2126
VL - 18
SP - 1463
EP - 1470
JO - Structure
JF - Structure
IS - 11
ER -