POLYMORPHIC VARIANTS IN HUMAN MUTY
POLYMORPHIC VARIANTS IN HUMAN MUTY
批准号:
2862030
负责人:
AMANDA K MCCULLOUGH
金额:
$28.52万
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-05-01 至 2002-04-30
关键词:
DNA damage DNA repair Escherichia coli HeLa cells N glycosidase cell population study enzyme activity enzyme structure genetic polymorphism genetic screening human tissue nucleic acid sequence oxidative stress polymerase chain reaction protein localization protein purification protein structure function site directed mutagenesis
中文摘要
描述(改编自研究者摘要)
英文摘要
DESCRIPTION (Adapted From the Investigator's Abstract)
Recent studies have demonstrated that genetic polymorphisms occur within the
genes that comprise the major DNA repair pathways. Mutations within many of
these genes can lead to increased toxicity and mutagenicity. Within the base
excision repair pathway, one of the primary DNA lesions that is repaired is an
oxidatively damaged guanine, 8-oxoG. The accumulation of this lesion has been
correlated with aging, cancer, neurodegeneration, and atherosclerosis. One of
the genes that is central to the efficient repair of this mismatch is the
adenine-specific DNA glycosylase, MutY, that removes adenine at A:8-oxoG
mispairs. The human MutY homolog, hMYH, has been cloned and potential
polymorphic variants identified. In order to determine the functional
significance of these and additional polymorphic variants in hMYH, three
independent laboratories have come together with diverse but complementary
expertise, to address this question. The first specific aim is to identify
additional polymorphic variants in the hMYE gene and these studies will be
carried out in the laboratory of H. Mohrenweiser. The choice of samples will
be a subset of those that have been preselected by NIH as being representative
of the U.S. population. All 16 exons and intron-exon junctions will be
analyzed from 96 genomic DNA samples. Specific aim 2 focuses on the
structure-function analysis of native hMYH and its polymorphic variants.
These studies will be guided and implemented in the laboratory of S. Lloyd,
based on the investigator's biochemical and x-ray crystallographic
determination of the prokaryotic MutY. The third specific aim, carried out in
the laboratory of I. Boldogh, will ascertain the role that cellular oxidative
stress has on the regulation and intracellular localization of hMYH.
Polymorphic variants that are not affected adversely, with respect to
catalysis, may be impaired in stabilization and localization. These goals
will be accomplished using a multidisciplinary collaborative approach
utilizing expertise in DNA repair enzymology, structure-function analysis,
polymorphic screening, and cell biology.
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Program in Biomedical Sciences
-
批准号:10620792
-
项目类别:
-
资助金额:$53.05万
-
财政年份:2021
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
Program in Biomedical Sciences
-
批准号:10270486
-
项目类别:
-
资助金额:$48.76万
-
财政年份:2021
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
Program in Biomedical Sciences
-
批准号:10439822
-
项目类别:
-
资助金额:$52.04万
-
财政年份:2021
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
DNA Repair Enzymes for the Prevention of Skin Cancer
-
批准号:7265086
-
项目类别:
-
资助金额:$10.0万
-
财政年份:2007
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
DNA Repair Enzymes for the Prevention of Skin Cancer
-
批准号:8337756
-
项目类别:
-
资助金额:$75.0万
-
财政年份:2005
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
DNA Repair Enzymes for the Prevention of Skin Cancer
-
批准号:8738036
-
项目类别:
-
资助金额:$3.62万
-
财政年份:2005
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
DNA Repair Enzymes for the Prevention of Skin Cancer
-
批准号:8608714
-
项目类别:
-
资助金额:$1.32万
-
财政年份:2005
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
DNA Repair Enzymes for the Prevention of Skin Cancer
-
批准号:8537720
-
项目类别:
-
资助金额:$1.67万
-
财政年份:2005
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
DNA Repair Enzymes for the Prevention of Skin Cancer
-
批准号:8198809
-
项目类别:
-
资助金额:$65.86万
-
财政年份:2005
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
POLYMORPHIC VARIANTS IN HUMAN MUTY
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批准号:6372416
-
项目类别:
-
资助金额:$22.12万
-
财政年份:1999
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
BASE FLIPPING AND DNA DAMAGE RECOGNITION
-
批准号:2909978
-
项目类别:
-
资助金额:$1.23万
-
财政年份:1999
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
POLYMORPHIC VARIANTS IN HUMAN MUTY
-
批准号:6169535
-
项目类别:
-
资助金额:$26.9万
-
财政年份:1999
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
BASE FLIPPING AND DNA DAMAGE RECOGNITION
-
批准号:2701312
-
项目类别:
-
资助金额:$3.55万
-
财政年份:1998
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
BASE FLIPPING AND DNA DAMAGE RECOGNITION
-
批准号:2018415
-
项目类别:
-
资助金额:$3.35万
-
财政年份:1997
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
STRUCTURAL STUDIES OF A MAMMALIAN APURINIC ENDONUCLEASE
-
批准号:2102477
-
项目类别:
-
资助金额:$1.78万
-
财政年份:1994
-
负责人:AMANDA K MCCULLOUGH
-
依托单位:
海外基金