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| 題名: | Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1 |
| 作者: | 簡汎清;Cheng, I-Cheng;Chen, Betty Chamay;Shuai, Hung-Hsun;Chien, Fan-Ching;Chen, Peilin;Hsieh, Tao-shih |
| 貢獻者: | 理學院光電科學與工程學系 |
| 關鍵詞: | Animals;Apoptosis;Carrier Proteins;Deoxyribonucleic acid;DNA;DNA damage;DNA repair;DNA Replication;Drosophila melanogaster;Drosophila Proteins;Enzymes;Flap Endonucleases - metabolism;Genetic research;Genomes;Genomic Instability;Genomics;GTP-Binding Proteins - metabolism;HCT116 Cells;Humans;Insects;Mice;Mice, Knockout;Microscopy;Mutation;Proliferating Cell Nuclear Antigen - metabolism;Proteins;Tumor Suppressor Protein p53 - metabolism |
| 日期: | 2016-01-11 |
| 上傳時間: | 2026-04-23 11:50:41 (UTC+8) |
| 出版者: | Public Library of Science;United States: Public Library of Science (PLoS) |
| 摘要: | 摘要： Replication forks are vulnerable to wayward nuclease activities. We report here our discovery of a new member in guarding genome stability at replication forks. We previously isolated a Drosophila mutation, wuho (wh, no progeny), characterized by a severe fertility defect and affecting expression of a protein (WH) in a family of conserved proteins with multiple WD40 repeats. Knockdown of WH by siRNA in Drosophila, mouse, and human cultured cells results in DNA damage with strand breaks and apoptosis through ATM/Chk2/p53 signaling pathway. Mice with mWh knockout are early embryonic lethal and display DNA damage. We identify that the flap endonuclease 1 (FEN1) is one of the interacting proteins. Fluorescence microscopy showed the localization of WH at the site of nascent DNA synthesis along with other replication proteins, including FEN1 and PCNA. We show that WH is able to modulate FEN1's endonucleolytic activities depending on the substrate DNA structure. The stimulatory or inhibitory effects of WH on FEN1's flap versus gap endonuclease activities are consistent with the proposed WH's functions in protecting the integrity of replication fork. These results suggest that wh is a new member of the guardians of genome stability because it regulates FEN1's potential DNA cleavage threat near the site of replication.
其他題名： PLoS Biol
出版者： United States: Public Library of Science (PLoS)
出版日期： 2016-01-01
出處： PLoS Biology, 2016-01, Vol.14 (1), p.e1002349
資源來源： EBSCOhost OmniFile Full Text Select
版權： COPYRIGHT 2016 Public Library of Science
版權： 2016 Cheng et al 2016 Cheng et al
版權： 2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Cheng I-C, Chen BC, Shuai H-H, Chien F-C, Chen P, Hsieh T-s (2016) Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1. PLoS Biol 14(1): e1002349. doi:10.1371/journal.pbio.1002349
識別號： ISSN: 1545-7885
識別號： ISSN: 1544-9173
識別號： EISSN: 1545-7885
識別號： DOI: 10.1371/journal.pbio.1002349
識別號： PMID: 26751069 |
| 顯示於類別: | [光電科學與工程學系] 期刊論文
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