TY - JOUR
T1 - Nucleotide insertion opposite a cis-syn thymine dimer by a replicative DNA polymerase from bacteriophage T7
AU - Li, Ying
AU - Dutta, Shuchismita
AU - Doublié, Sylvie
AU - Bdour, Hussam Moh d.
AU - Taylor, John Stephen
AU - Ellenberger, Tom
N1 - Funding Information:
We thank our colleagues for help with X-ray data collection and stimulating discussions. Thanks to the staff at beamlines X-12C and X-25 of the National Synchrotron Light Source and beamline F1 of the Cornell High Energy Synchrotron Source for their assistance with X-ray data collection. This work was funded by research grants R01 GM55390 (to T.E.) and R01 CA40463 (to J.-S.T.), and by funding from the Giovanni Armenise Harvard Center for Structural Biology. Y.L. is a US National Institutes of Health Ruth L. Kirschstein postdoctoral fellow (F32 GM065746). T.E.E. is the Hsien Wu and Daisy Yen Wu professor at Harvard Medical School.
PY - 2004/8
Y1 - 2004/8
N2 - Ultraviolet-induced DNA damage poses a lethal block to replication. To understand the structural basis for this, we determined crystal structures of a replicative DNA polymerase from bacteriophage T7 in complex with nucleotide substrates and a DNA template containing a cis-syn cyclobutane pyrimidine dimer (CPD). When the 3′ thymine is the templating base, the CPD is rotated out of the polymerase active site and the fingers subdomain adopts an open orientation. When the 5′ thymine is the templating base, the CPD lies within the polymerase active site where it base-pairs with the incoming nucleotide and the 3′ base of the primer, while the fingers are in a closed conformation. These structures reveal the basis for the strong block of DNA replication that is caused by this photolesion.
AB - Ultraviolet-induced DNA damage poses a lethal block to replication. To understand the structural basis for this, we determined crystal structures of a replicative DNA polymerase from bacteriophage T7 in complex with nucleotide substrates and a DNA template containing a cis-syn cyclobutane pyrimidine dimer (CPD). When the 3′ thymine is the templating base, the CPD is rotated out of the polymerase active site and the fingers subdomain adopts an open orientation. When the 5′ thymine is the templating base, the CPD lies within the polymerase active site where it base-pairs with the incoming nucleotide and the 3′ base of the primer, while the fingers are in a closed conformation. These structures reveal the basis for the strong block of DNA replication that is caused by this photolesion.
UR - https://www.scopus.com/pages/publications/3543002207
U2 - 10.1038/nsmb792
DO - 10.1038/nsmb792
M3 - Article
C2 - 15235589
AN - SCOPUS:3543002207
SN - 1545-9993
VL - 11
SP - 784
EP - 790
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 8
ER -