Keyword search (4,163 papers available)

"O'Flaherty DK" Authored Publications:

Title Authors PubMed ID
1 O4-alkyl-2'-deoxythymidine cross-linked DNA to probe recognition and repair by O6-alkylguanine DNA alkyltransferases. McManus FP, O'Flaherty DK, Noronha AM, Wilds CJ 22850722
CHEMBIOCHEM
2 Backbone Flexibility Influences Nucleotide Incorporation by Human Translesion DNA Polymerase η opposite Intrastrand Cross-Linked DNA. O'Flaherty DK, Guengerich FP, Egli M, Wilds CJ 26624500
CHEMBIOCHEM
3 O(6)-Alkylguanine DNA Alkyltransferase Repair Activity Towards Intrastrand Cross-Linked DNA is Influenced by the Internucleotide Linkage. O'Flaherty DK, Wilds CJ 26692563
CHEMISTRY
4 Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase η. O'Flaherty DK, Patra A, Su Y, Guengerich FP, Egli M, Wilds CJ 27574558
CHEMBIOCHEM
5 Preparation of Intrastrand {G}O(6) -Alkylene-O(6) {G} Cross-Linked Oligonucleotides. O'Flaherty DK, Wilds CJ 27584704
CHEMBIOCHEM
6 O6-2'-Deoxyguanosine-butylene-O6-2'-deoxyguanosine DNA Interstrand Cross-Links Are Replication-Blocking and Mutagenic DNA Lesions. Xu W, Kool D, O'Flaherty DK, Keating AM, Sacre L, Egli M, Noronha A, Wilds CJ, Zhao L 27768841
CHEMBIOCHEM
7 Site-specific covalent capture of human O6-alkylguanine-DNA-alkyltransferase using single-stranded intrastrand cross-linked DNA. O'Flaherty DK, Wilds CJ 27886318
CHEMBIOCHEM
8 Structural basis of interstrand cross-link repair by O6-alkylguanine DNA alkyltransferase. Denisov AY, McManus FP, O'Flaherty DK, Noronha AM, Wilds CJ 28937154
CHEMBIOCHEM
9 AGT Activity Towards Intrastrand Crosslinked DNA is Modulated by the Alkylene Linker. O'Flaherty DK, Wilds CJ 28980757
CHEMBIOCHEM
10 Altering Residue 134 Confers an Increased Substrate Range of Alkylated Nucleosides to the E. coli OGT Protein. Schoonhoven NM, O'Flaherty DK, McManus FP, Sacre L, Noronha AM, Kornblatt MJ, Wilds CJ 29137116
CHEMBIOCHEM
11 Covalent capture of OGT's active site using engineered human-E. coli chimera and intrastrand DNA cross-links. Copp W, O'Flaherty DK, Wilds CJ 30430154
CHEMBIOCHEM

 

Title:Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase η.
Authors:O'Flaherty DK,  Patra A,  Su Y,  Guengerich FP,  Egli M,  Wilds CJ
Link:https://www.ncbi.nlm.nih.gov/pubmed/27574558?dopt=Abstract
Publication:
Keywords:
PMID:27574558 Category:Chem Sci Date Added:2019-05-31
Dept Affiliation: CHEMBIOCHEM
1 Department of Chemistry and Biochemistry, Concordia University, Montréal, Québec H4B1R6, Canada.
2 Department of Biochemistry, Vanderbilt Institute of Chemical Biology, and Center for Structural Biology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, United States.

Description:

Lesion Orientation of O4-Alkylthymidine Influences Replication by Human DNA Polymerase ?.

Chem Sci. 2016 Aug 01;7(8):4896-4904

Authors: O'Flaherty DK, Patra A, Su Y, Guengerich FP, Egli M, Wilds CJ

Abstract

DNA lesions that elude repair may undergo translesion synthesis catalyzed by Y-family DNA polymerases. O4-Alkylthymidines, persistent adducts that can result from carcinogenic agents, may be encountered by DNA polymerases. The influence of lesion orientation around the C4-O4 bond on processing by human DNA polymerase ? (hPol ?) was studied for oligonucleotides containing O4-methylthymidine, O4-ethylthymidine, and analogs restricting the O4-methylene group in an anti-orientation. Primer extension assays revealed that the O4-alkyl orientation influences hPol ? bypass. Crystal structures of hPol ?•DNA•dNTP ternary complexes with O4-methyl- or O4-ethylthymidine in the template strand showed the nucleobase of the former lodged near the ceiling of the active site, with the syn-O4-methyl group engaged in extensive hydrophobic interactions. This unique arrangement for O4-methylthymidine with hPol ?, inaccessible for the other analogs due to steric/conformational restriction, is consistent with differences observed for nucleotide incorporation and supports the concept that lesion conformation influences extension across DNA damage. Together, these results provide mechanistic insights on the mutagenicity of O4MedT and O4EtdT when acted upon by hPol ?.

PMID: 27574558 [PubMed - as supplied by publisher]




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