Abstract

The DNA Synthesis Resource Core plays an essential role in the successful integration of this Program Project by providing high purity, site-specifically modified oligonucleotides to Projects 1, 2 and 3. The DNA Synthesis Resource Core works closely with Project 1, where novel reagents and synthetic strategies are developed for the site-specific synthesis of oligonucleotides containing the Fapy-dG lesions of interest to the Program ProjecL The technology is transferred to the Core, where the desired modified oligonucleotides are synthesized on the appropriate scale and purity for further chemical and replication studies by Project 1, cell-based studies by Project 2, and structural studies by Project 3.
The Specific Aims for the DNA Synthesis Resource Core are: 1) to synthesize the phosphoramidite reagents of the various Fapy-dG lesions and Incorporate them into oligonucleotides;2) develop protocols for the purification of the modified oligonucleotides;and 3) provide initial characterization of modified oligonucleotide.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA160032-21A1
Application #
8369644
Study Section
Special Emphasis Panel (ZCA1-RPRB-O (M1))
Project Start
1997-08-01
Project End
2017-07-31
Budget Start
2012-09-20
Budget End
2013-07-31
Support Year
21
Fiscal Year
2012
Total Cost
$85,349
Indirect Cost
$20,354

  Institution

Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212

  Publications

Sha, Yan; Minko, Irina G; Malik, Chanchal K et al. (2017) Error-prone replication bypass of the imidazole ring-opened formamidopyrimidine deoxyguanosine adduct. Environ Mol Mutagen 58:182-189
Minko, Irina G; Rizzo, Carmelo J; Lloyd, R Stephen (2017) Mutagenic potential of nitrogen mustard-induced formamidopyrimidine DNA adduct: Contribution of the non-canonical ?-anomer. J Biol Chem 292:18790-18799
Su, Yan; Egli, Martin; Guengerich, F Peter (2017) Human DNA polymerase ? accommodates RNA for strand extension. J Biol Chem 292:18044-18051
Patra, Amritraj; Politica, Dustin A; Chatterjee, Arindom et al. (2016) Mechanism of Error-Free Bypass of the Environmental Carcinogen N-(2'-Deoxyguanosin-8-yl)-3-aminobenzanthrone Adduct by Human DNA Polymerase??. Chembiochem 17:2033-2037
Choi, Jeong-Yun; Patra, Amritaj; Yeom, Mina et al. (2016) Kinetic and Structural Impact of Metal Ions and Genetic Variations on Human DNA Polymerase ?. J Biol Chem 291:21063-21073
Minko, Irina G; Jacobs, Aaron C; de Leon, Arnie R et al. (2016) Catalysts of DNA Strand Cleavage at Apurinic/Apyrimidinic Sites. Sci Rep 6:28894
Patra, Amritraj; Su, Yan; Zhang, Qianqian et al. (2016) Structural and Kinetic Analysis of Miscoding Opposite the DNA Adduct 1,N6-Ethenodeoxyadenosine by Human Translesion DNA Polymerase ?. J Biol Chem 291:14134-45
Su, Yan; Egli, Martin; Guengerich, F Peter (2016) Mechanism of Ribonucleotide Incorporation by Human DNA Polymerase ?. J Biol Chem 291:3747-56
Xu, Wenyan; Kool, Daniel; O'Flaherty, Derek K et al. (2016) O6-2'-Deoxyguanosine-butylene-O6-2'-deoxyguanosine DNA Interstrand Cross-Links Are Replication-Blocking and Mutagenic DNA Lesions. Chem Res Toxicol 29:1872-1882
Patra, Amitraj; Zhang, Qianqian; Guengerich, F Peter et al. (2016) Mechanisms of Insertion of dCTP and dTTP Opposite the DNA Lesion O6-Methyl-2'-deoxyguanosine by Human DNA Polymerase ?. J Biol Chem 291:24304-24313

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