Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

N2 ALKYIG ADDUCTS--MUTATIONS AND POLYMERASE INTERACTIONS

Award Number: R01CA088950
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2001
PERIOD OF PERFORMANCE END DATE: 01/31/2005

Group Awards By:

View Award Description

N2 ALKYIG ADDUCTS--MUTATIONS AND POLYMERASE INTERACTIONS - DESCRIPTION: (Adapted from the investigator's abstract) Recent evidence indicates that guanine N2 adducts form in the presence of ethanol or carcinogens that alkylate DNA with >3 carbon alkyl groups. It is anticipated that N2-alkylguanine adducts will significantly perturb DNA replication because the alkyl group is in position to alter Watson-Crick base pairing; however, at present there are no data addressing replication of DNA containing N2-alkylguanine, nor is it known if or how these adducts are repaired. This proposal will close that gap in our understanding of DNA alkylator-induced mutagenesis by: 1) Oligodeoxyribonucleotides containing single N2-ethylguanine, N2-isopropylguanine, O6-ethyl guanine, and O6-isopropylguanine bases will be synthesized. 2) Oligonucleotides containing these four guanine adducts will be used as templates for DNA polymerization catalyzed in vitro by purified human DNA polymerase a, q, e, and n. Polymerase m is a recently discovered "bypass" human DNA polymerase thought to be involved in replication across blocking lesions. These experiments will compare the coding and extension properties of the N2 vs. O6 alkylguanine adducts. 3) Oligonucleotides containing these four alkylguanine adducts will be incorporated site specifically into the double stranded mutation reporting shuttle plasmid pLS189. The mutation frequency and spectra induced in vivo by the N2 vs. O6 alkylguanine adducts will be determined after replication of the plasmid in normal and nucleotide excision repair (NER)-deficient human fibroblasts. The role of NER in modulating mutagenesis by these adducts can thereby be determined. 4) The question of whether the N2-alkylguanine adducts are repaired by short patch base excision repair will be addressed by incubating extracts of NER-deficient human fibroblasts with alkylguanine-containing double-stranded oligonucleotides and determining incorporation of (32P)-dGTP at the adducted position. The data provided by this proposal will gauge the biologic impact of previously unexplored N2-alkylguanine adducts in comparison to the better known mutagenic O6-alkylguanine adducts.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2004 ( Subtotal = $168,811 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Cause and Prevention Research	000	4	1/8/2004	NON-COMPETING CONTINUATION	$168,811
														Subtotal = $168,811

Issue Date FY: 2003 ( Subtotal = $197,029 )
2003	2003	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Cancer Cause and Prevention Research	000	3		NON-COMPETING CONTINUATION	$197,029
														Subtotal = $197,029

Issue Date FY: 2002 ( Subtotal = $220,468 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Cancer Cause and Prevention Research	000	2	1/31/2002	NON-COMPETING CONTINUATION	$220,468
														Subtotal = $220,468

Issue Date FY: 2001 ( Subtotal = $323,103 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Cancer Biology Research	000	1	4/4/2001	NEW	$323,103
														Subtotal = $323,103

Grand Total All Awards = $909,411

Top

All Categories

About

Search

Reports

Data Submission

Award Information

N2 ALKYIG ADDUCTS--MUTATIONS AND POLYMERASE INTERACTIONS

Award Number: R01CA088950

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2001

PERIOD OF PERFORMANCE END DATE: 01/31/2005

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer