{"id":{"repo_id":"maryland","oai_identifier":"oai:drum.lib.umd.edu:1903/9706"},"canonical_url":"https://search.dev.ndltd.org/etd/maryland/oai:drum.lib.umd.edu:1903/9706","repository":{"repo_id":"maryland","name":"University of Maryland","base_url":"https://api.drum.lib.umd.edu/server/oai/request"},"display":{"title":"THE FUNCTION OF MRN (MRE11-RAD50-NBS1) COMPLEX DURING WRN (WERNER) FACILITATED ATM (ATAXIA-TELANGIECTASIA MUTATED) ACTIVATION","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Ma, Junhao"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Nutrition","school":null,"contributors":[],"advisors":["Cheng, Wen-Hsing"],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-24T03:02:27Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1903/9706","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Cheng, Wen-Hsing"]},{"key":"dc:contributor.department","label":"Department","values":["Nutrition"]},{"key":"dc:creator","label":"Author","values":["Ma, Junhao"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2009-11-06T06:30:55Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2009-11-06T06:30:55Z"]},{"key":"dc:date.issued","label":"Date","values":["2009"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1903/9706"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:title","label":"Title","values":["THE FUNCTION OF MRN (MRE11-RAD50-NBS1) COMPLEX DURING WRN (WERNER) FACILITATED ATM (ATAXIA-TELANGIECTASIA MUTATED) ACTIVATION"]}]}],"canonical_facts":{"dc:contributor.advisor":["Cheng, Wen-Hsing"],"dc:contributor.department":["Nutrition"],"dc:creator":["Ma, Junhao"],"dc:date.accessioned":["2009-11-06T06:30:55Z"],"dc:date.available":["2009-11-06T06:30:55Z"],"dc:date.issued":["2009"],"dc:description.abstract":["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."],"dc:identifier.uri":["http://hdl.handle.net/1903/9706"],"dc:title":["THE FUNCTION OF MRN (MRE11-RAD50-NBS1) COMPLEX DURING WRN (WERNER) FACILITATED ATM (ATAXIA-TELANGIECTASIA MUTATED) ACTIVATION"],"dc:type":["Thesis"]},"updated_at":"2026-07-24T03:02:27Z"}