Ubiquitin-mediated regulation of the RAD51D homologous recombination protein
Ubiquitin-mediated regulation of the RAD51D homologous recombination protein
批准号:
8689271
负责人:
DOUGLAS Lee PITTMAN
金额:
$32.53万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-09-01 至 2018-08-31
关键词:
Alternative SplicingAmino AcidsAntineoplastic AgentsBRCA1 geneBRCA2 geneBiologyBiomedical ResearchCancer-Predisposing GeneCarcinogenesis MechanismCellular biologyChromosomal StabilityClinicCo-ImmunoprecipitationsComplexConfocal MicroscopyCongenital AbnormalityDNADNA DamageDNA Interstrand CrosslinkingDataDefectDevelopmentDoctor of PharmacyDouble Strand Break RepairDrug TargetingEnzymesExposure toFamily memberFellowshipGenesGeneticGenomeGenomic InstabilityHuman GenomeIndividualInfertilityInstitutionLaboratoriesLysineMalignant NeoplasmsMalignant neoplasm of ovaryMass Spectrum AnalysisMediatingMinorityMutationNew YorkPathway interactionsPharmacologic SubstancePharmacy StudentsPhenotypePost-Translational Protein ProcessingPremature aging syndromeProcessProgram ReviewsProtein IsoformsProteinsRad51 recombinaseRecruitment ActivityRegulationResearchResearch TrainingScienceScientistSiteSouth CarolinaTechniquesTestingTexasTrainingUbiquitinUbiquitinationUnderrepresented MinorityUniversitiesYeastscancer cellchemotherapycollegedemographicsenvironmental agentexperiencegraduate studenthigh schoolhomologous recombinationmembermulticatalytic endopeptidase complexmutantnovelprogramsprotein functionpublic health relevancerepairedresearch studyresponseteachertoolubiquitin-protein ligaseundergraduate studentyeast two hybrid system
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Mutations in RAD51 genes confer genome instability phenotypes associated with infertility, birth defects, and
cancer. Each of the RAD51 family members are central components of the error-free double strand break
(DSB) repair pathway known as homologous recombination (HR), and RAD51D was recently identified as an
ovarian cancer susceptibility gene. Even though it is known that HR defects predispose individuals to
malignancy and confers cancer cell sensitivity to DNA damaging chemotherapy agents, single-protein analyses
have revealed little functional information. Therefore, we performed RAD51D protein interaction screens and
identified RNF138, a novel RING domain E3 ubiquitin ligase enzyme. Ubiquitin is a 76-amino acid protein that
modifies protein functions or marks them for proteasome degradation, leading to the central hypothesis of this
application: RAD51D forms adaptive complexes that are tightly regulated by RNF138 to process DNA breaks
and maintain genome integrity. To test this hypothesis, the first aim will determine how RNF138 and RAD51D
interaction regulates the HR DNA damage response pathway. The second aim will identify the ubiquitin linkage
arrangements and sites along the RAD51D protein and their association with DNA damage response. Over the
course of this project, undergraduate, graduate, and Doctor of Pharmacy students will receive outstanding
biomedical research training. Undergraduate students are recruited from the highly selective University of
South Carolina Honors College, which is ranked first by the Public University Honors Program "Review of Fifty
Public University Honors Programs." Therefore, investigating RAD51D post-translational modifications will
uncover mechanisms of carcinogenesis pathways and identify potential cancer drug targets as well as provide
training in state-of-the-art biomedical science techniques.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1007/978-1-4939-9500-4_1
发表时间:
2019
期刊:
Methods in molecular biology
影响因子:
--
作者:
[N. M. Reilly;B. Yard;D. Pittman]
通讯作者:
N. M. Reilly;B. Yard;D. Pittman
DOI:
10.1016/j.dnarep.2016.04.006
发表时间:
2016-06
期刊:
DNA repair
影响因子:
3.8
作者:
[Yard BD, Reilly NM, Bedenbaugh MK, Pittman DL]
通讯作者:
Pittman DL
MEIOTIC RECOMBINATION IN THE MOUSE
-
批准号:2872621
-
项目类别:
-
资助金额:$2.91万
-
财政年份:1998
-
负责人:DOUGLAS Lee PITTMAN
-
依托单位:
MEIOTIC RECOMBINATION IN THE MOUSE
-
批准号:2417134
-
项目类别:
-
资助金额:$2.54万
-
财政年份:1998
-
负责人:DOUGLAS Lee PITTMAN
-
依托单位:
海外基金