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oai:drum.lib.umd.edu:1903/97062016-03-29T05:31:06Zcom_1903_2267com_1903_1598com_1903_2col_1903_2798col_1903_3

Cheng, Wen-Hsing Ma, Junhao Digital Repository at the University of Maryland University of Maryland (College Park, Md.) Nutrition 2009-11-06T06:30:55Z 2009-11-06T06:30:55Z 2009 http://hdl.handle.net/1903/9706 WRN (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. THE FUNCTION OF MRN (MRE11-RAD50-NBS1) COMPLEX DURING WRN (WERNER) FACILITATED ATM (ATAXIA-TELANGIECTASIA MUTATED) ACTIVATION Thesis Health Sciences, Nutrition Biology, Cell Biology, Genetics ATM MRN complex NBS1 WRN open.access