This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cellular DNA is constantly challenged by endogenous and exogenous chemicals, often resulting in cytotoxic and/or mutagenic covalent adducts. Alkylating agents are one group of such chemicals widely used in clinical settings and prevalent in the environment that create cytotoxic DNA lesions. Once damaged, cellular DNA must be promptly repaired. Organisms have evolved a variety of mechanisms to repair these cytotoxic/mutagenic damages. In E. coli, AlkB protein is one of the four proteins that are activated when E. coli is challenged with high doses of methylation agents. It belongs to a dioxygenase family that uses a non-heme mononuclear iron(II) and cofactors 2-ketoglutarate (2-KG) and dioxygen to perform an oxidative demethylation of DNA base lesions 1-meA and 3-meC. AlkB could also repair ethenoA, N3-methylthyine (3-meT), and N1-methylguanine (1-meG) using the same oxidation mechanism albeit with a lower activity. There are nine human homologues of AlkB, ABH1-8 and FTO, which have been identified through sequence alignment. Biochemical characterizations indicate that ABH2, ABH3, FTO and ABH1 possess some of the DNA/RNA base demethylation activity of AlkB. Some of these proteins play critical roles in various functions in human cells, and impacting diseases such as cancers and obesity. We have been working on structural characterization of this family of very important nucleic acid demethylases.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR015301-09
Application #
8361674
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-04-01
Project End
2012-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
9
Fiscal Year
2011
Total Cost
$10,975
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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