Depletion of tyrosyl DNA phosphodiesterase 2 activity enhances etoposide-mediated double-strand break formation and cell killing
详细信息 查看全文
- 作者：Yasemin Saygideger Konta ; b ; 1 ; ys452@georgetown.edu" class="auth_mail" title="E-mail the corresponding author ; Arijit Duttac ; d ; 1 ; ardutta@utmb.edu" class="auth_mail" title="E-mail the corresponding author ; Apurva Mallisettya ; 1 ; apurva.mallisetty@gmail.com" class="auth_mail" title="E-mail the corresponding author ; Jeena Mathewa ; jm722@georgetown.edu" class="auth_mail" title="E-mail the corresponding author ; Tsion Minasa ; tm484@georgetown.edu" class="auth_mail" title="E-mail the corresponding author ; Christina Krausa ; cnk10@georgetown.edu" class="auth_mail" title="E-mail the corresponding author ; Priyanka Dhopeshwarkara ; 2 ; priyanka.dhopeshwarkar@ablinc.com" class="auth_mail" title="E-mail the corresponding author ; Bhaskar Kallakurye ; kallakub@georgetown.edu" class="auth_mail" title="E-mail the corresponding author ; Sankar Mitrac ; smitra2@houstonmethodist.org" class="auth_mail" title="E-mail the corresponding author ; Aykut Ü ; rena ; au26@georgetown.edu" class="auth_mail" title="E-mail the corresponding author ; Sanjay Adhikarif ; sadhikari@houstonmethodist.org" class="auth_mail" title="E-mail the corresponding author
- 关键词：DNA repair ; Enzyme assay ; TDP2 ; High throughput screening ; Molecular probe ; Inhibitor ; NSC111041
- 刊名：DNA Repair
- 出版年：2016
- 出版时间：July 2016
- 年：2016
- 卷：43
- 期：Complete
- 页码：38-47
- 全文大小：3100 K
文摘
- class="listitem" id="list_lis0005">
- class="label">•
TDP2 confers resistance of tumor cells to Top2-poisons by repairing such covalent DNA-protein adducts, and its pharmacological inhibition could enhance the efficacy of Top2-poisons.
- class="label">•
We discovered NSC111041, a selective inhibitor of TDP2, by optimizing a high throughput screening (HTS) assay for TDP2’s 5′-tyrosyl phosphodiesterase activity and subsequent validation studies.
- class="label">•
We found that NSC111041 inhibits TDP2’s binding to DNA without getting intercalated into DNA and enhanced etoposide’s cytotoxicity synergistically in TDP2-expressing cells but not in TDP2 depleted cells.