? CORE A The four research projects of the Program Project propose laboratory characterization of the consequences of genetic variation for carcinogenesis and cancer therapy. These studies are focused on genes involved in Base Excision Repair (BER). Genetic variation will include germline and somatic variation. Core A will provide informatics and statistics support for these experiments. Core A personnel have expertise in bioinformatics, systems biology, statistics, process management, and high performance computing. Dr. Bond has worked with the P01 since its inception.
Aim 1 (Informatics) Identify variants for functional studies. A central role of Core A is to support identification of variants, for experimental studies, that are expected to have consequences for protein function. These variants are identified using DNA sequences available from large- scale sequence projects such as the 1000 Genomes Project and The Cancer Genome Atlas. Core A annotates the variants using publicly available software. Core A (Drs. Bond and Dragon) host weekly meetings at which these variants are presented and discussed. These meetings provide consistent communications with members of the four projects.
Aim 2 (Statistics) Provide software and statistical support for hypothesis tests. The laboratory studies proposed in Projects 1-4 will characterize the consequences of this variation for protein structure, interactions, damage search and catalysis as well as cellular proliferation and survival. Core A statistical services will support design and analysis of these experiments.

Public Health Relevance

Experiments proposed by the Program Project characterize the consequences of natural human genetic variation in Base Excision Repair enzymes for carcinogenesis and cancer therapy. Core A provides informatics and statistics services that support design and analysis of these experiments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA098993-11A1
Application #
9209392
Study Section
Special Emphasis Panel (ZCA1-RPRB-F (O1))
Project Start
2004-09-03
Project End
2022-04-30
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
11
Fiscal Year
2017
Total Cost
$114,814
Indirect Cost
$41,097
Name
University of Vermont & St Agric College
Department
Type
Domestic Higher Education
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
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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
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
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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
Marsden, Carolyn G; Jensen, Ryan B; Zagelbaum, Jennifer et al. (2016) The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype. PLoS Genet 12:e1006208
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Cannan, Wendy J; Pederson, David S (2016) Mechanisms and Consequences of Double-Strand DNA Break Formation in Chromatin. J Cell Physiol 231:3-14
Silva, Michelle C; Morrical, Milagros D; Bryan, Katie E et al. (2016) RAD51 variant proteins from human lung and kidney tumors exhibit DNA strand exchange defects. DNA Repair (Amst) 42:44-55

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