The overall goal of this Program Project is to understand at the atomic level how three families of DNA repair enzymes recognize and process their substrates. The central goal of the Bioinformatics Core is to make use of sequence, structure, and function data for the design and interpretation of experiments that will achieve the goal of the Program Project.
The Aims of the Research Projects involve testing hypotheses about natural enzymes and site-directed mutants of these enzymes using functional measurements and X-ray crystallography. The Bioinformatics Core will provide tools that use existing knowledge of the structure and function of these families to identify natural enzymes and site-directed mutants for these studies. The results of the experimental work will be used by the Bioinformatics Core for designing subsequent experiments.
The Aims of the Bioinformatics Core are:
Aim 1 : To provide infrastructure for information management and analysis. The Core will provide stable and secure information management as well as flexible querying mechanisms and a broad spectrum of bioinformatics tools. The information will include primary data, experimental designs, and inferred results. The analysis tools will include existing applications and custom analysis tools that enhance research productivity.
Aim 2 : To develop phylogenetic tree-based methods for selecting natural enzymes for functional and structural studies.
Aim 3 : To develop phylogenetic tree-based methods for selecting site-directed mutants of natural enzymes for functional and structural studies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
1P01CA098993-01A2
Application #
6997985
Study Section
Subcommittee G - Education (NCI)
Project Start
2004-09-03
Project End
2009-08-31
Budget Start
2004-09-03
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$151,562
Indirect Cost
Name
University of Vermont & St Agric College
Department
Type
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Maher, R L; Marsden, C G; Averill, A M et al. (2017) Human cells contain a factor that facilitates the DNA glycosylase-mediated excision of oxidized bases from occluded sites in nucleosomes. DNA Repair (Amst) 57:91-97
Marsden, Carolyn G; Dragon, Julie A; Wallace, Susan S et al. (2017) Base Excision Repair Variants in Cancer. Methods Enzymol 591:119-157
Galick, Heather A; Marsden, Carolyn G; Kathe, Scott et al. (2017) The NEIL1 G83D germline DNA glycosylase variant induces genomic instability and cellular transformation. Oncotarget 8:85883-85895
Robey-Bond, Susan M; Benson, Meredith A; Barrantes-Reynolds, Ramiro et al. (2017) Probing the activity of NTHL1 orthologs by targeting conserved amino acid residues. DNA Repair (Amst) 53:43-51
Cannan, Wendy J; Rashid, Ishtiaque; Tomkinson, Alan E et al. (2017) The Human Ligase III?-XRCC1 Protein Complex Performs DNA Nick Repair after Transient Unwrapping of Nucleosomal DNA. J Biol Chem 292:5227-5238
Silva, Michelle C; Bryan, Katie E; Morrical, Milagros D et al. (2017) Defects in recombination activity caused by somatic and germline mutations in the multimerization/BRCA2 binding region of human RAD51 protein. DNA Repair (Amst) 60:64-76
Zhou, Jia; Chan, Jany; Lambelé, Marie et al. (2017) NEIL3 Repairs Telomere Damage during S Phase to Secure Chromosome Segregation at Mitosis. Cell Rep 20:2044-2056
Prakash, Aishwarya; Moharana, Kedar; Wallace, Susan S et al. (2017) Destabilization of the PCNA trimer mediated by its interaction with the NEIL1 DNA glycosylase. Nucleic Acids Res 45:2897-2909
Lee, Andrea J; Wallace, Susan S (2017) Hide and seek: How do DNA glycosylases locate oxidatively damaged DNA bases amidst a sea of undamaged bases? Free Radic Biol Med 107:170-178
Lee, Andrea J; Wallace, Susan S (2016) Visualizing the Search for Radiation-damaged DNA Bases in Real Time. Radiat Phys Chem Oxf Engl 1993 128:126-133

Showing the most recent 10 out of 64 publications