Supplementary Methods and Materials, Figures 1-5 from Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection

Peng, Guang; Dai, Hui; Zhang, Wei; Hsieh, Hui-Ju; Pan, Mei-Ren; Park, Yun-Yong; Tsai, Robert Yu-Lin; Bedrosian, Isabelle; Lee, Ju-Seog; Ira, Grzegorz; Lin, Shiaw-Yih

doi:10.1158/0008-5472.22390299.v1

Supplementary Methods and Materials, Figures 1-5 from Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection

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posted on 2023-03-30, 20:46 authored by Guang Peng, Hui Dai, Wei Zhang, Hui-Ju Hsieh, Mei-Ren Pan, Yun-Yong Park, Robert Yu-Lin Tsai, Isabelle Bedrosian, Ju-Seog Lee, Grzegorz Ira, Shiaw-Yih Lin

PDF file - 633K, Supplementary Fig 1: DNA2 associates with replication forks and prevents the accumulation of replication-associated DSBs. S. Fig 2: DNA2 facilitates HR repair. S. Fig 3: DNA2's function in HR repair is dependent on its nuclease activity. S. Fig 4: Biological effects of DNA2 depletion on cancer cells. S. Fig 5: Effects of DNA2 depletion on the generation of ROS. PLUS supplemental Materials and Methods

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ARTICLE ABSTRACT

In precancerous and cancerous lesions, excessive growth signals resulting from activation of oncogenes or loss of tumor suppressor genes lead to intensive replication stress, which is recognized by a high level of replication-associated DNA double-strand breaks (DSB). However, the molecular mechanism by which cells alleviate excessive replication stress remains unclear. In this study, we report that the human nuclease/helicase DNA2 facilitates homologous recombination to repair replication-associated DNA DSBs, thereby providing cells with survival advantages under conditions of replication stress. The nuclease activity of DNA2 was required for DSB end resection, which allowed subsequent recruitment of RPA and RAD51 to repair DSBs and restart replication. More importantly, DNA2 expression was significantly increased in human cancers and its expression correlated with patient outcome. Our findings therefore indicate that enhanced activity of DSB resection likely constitutes one mechanism whereby precancerous and cancerous cells might alleviate replication stress. Cancer Res; 72(11); 2802–13. ©2012 AACR.

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Breast Cancer Carcinogenesis DNA damage and repair Gastrointestinal Cancers Pancreatic cancer

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Supplementary Methods and Materials, Figures 1-5 from Human Nuclease/Helicase DNA2 Alleviates Replication Stress by Promoting DNA End Resection

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