THE FUNCTION OF MRN (MRE11-RAD50-NBS1) COMPLEX DURING WRN (WERNER) FACILITATED ATM (ATAXIA-TELANGIECTASIA MUTATED) ACTIVATION

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dc.contributor.advisorCheng, Wen-Hsingen_US
dc.contributor.authorMa, Junhaoen_US
dc.contributor.departmentNutritionen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2009-11-06T06:30:55Z
dc.date.available2009-11-06T06:30:55Z
dc.date.issued2009en_US
dc.description.abstractWRN (Werner) protein is a member of the RecQ family showing helicase and exonuclease activity. WRN protein may lose function upon mutation and causes Werner syndrome (WS) which is an autosomal recessive, cancer-prone and premature aging disease. ATM (Ataxia-Telangiectasia mutated) protein initiates a signaling pathway in response to DNA double strand breaks (DSBs). Genomic disorder ataxia-telangiectasia (A-T) is associated with defective ATM. WRN protein is involved in ATM pathway activation when cells are exposed to DSBs associated with replication fork collapse. Because the Mre11-Rad50-Nbs1 (MRN) complex, a sensor of DSBs, is known to interact with WRN and ATM, we investigated whether the MRN complex mediates the WRN-dependent ATM pathway activation. In this study, we employed short-hairpin RNA to generate WRN- and Nbs1-deficient U-2 OS (osteosarcoma) cells. Cells were treated with clastogens which induce collapsed replication forks, thus provided proof for whether WRN facilitates ATM activation via MRN complex. This study serves as a basis for future investigation on the correlation between ATM, MRN complex and WRN, which will ultimately help understand the mechanism of aging and cancer.en_US
dc.identifier.urihttp://hdl.handle.net/1903/9706
dc.subject.pqcontrolledHealth Sciences, Nutritionen_US
dc.subject.pqcontrolledBiology, Cellen_US
dc.subject.pqcontrolledBiology, Geneticsen_US
dc.subject.pquncontrolledATMen_US
dc.subject.pquncontrolledMRN complexen_US
dc.subject.pquncontrolledNBS1en_US
dc.subject.pquncontrolledWRNen_US
dc.titleTHE FUNCTION OF MRN (MRE11-RAD50-NBS1) COMPLEX DURING WRN (WERNER) FACILITATED ATM (ATAXIA-TELANGIECTASIA MUTATED) ACTIVATIONen_US
dc.typeThesisen_US

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