<br>FANCI/FANCD2 复合物通过 SRSF1 介导的 mRNA 输出将 DNA 损伤反应与 R 环调节联系起来,Cell Reports

当前位置： X-MOL 学术 › Cell Rep. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

FANCI/FANCD2 复合物通过 SRSF1 介导的 mRNA 输出将 DNA 损伤反应与 R 环调节联系起来
Cell Reports ( IF 7.5 ) Pub Date : 2024-01-01 , DOI: 10.1016/j.celrep.2023.113610
Anne Olazabal-Herrero ₁ , Boxue He ₂ , Youngho Kwon ₃ , Abhishek K Gupta ₄ , Arijit Dutta ₃ , Yuxin Huang ₃ , Prajwal Boddu ₄ , Zhuobin Liang ₅ , Fengshan Liang ₁ , Yaqun Teng ₆ , Li Lan ₆ , Xiaoyong Chen ₇ , Huadong Pei ₈ , Manoj M Pillai ₄ , Patrick Sung ₃ , Gary M Kupfer ₉

Affiliation

Department of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA; Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Department of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, New Haven, CT 06511, USA.
Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen 518132, China.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, USA; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06511, USA.
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
Department of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.

范可尼贫血（FA）的特征是先天性异常、骨髓衰竭和癌症易感性。中央 FA 蛋白复合物 FANCI/FANCD2 （ID2）被单泛素化激活，并募集 DNA 修复蛋白用于链间交联（ICL）修复和复制叉保护。FA 通路的缺陷导致 R 环积累，从而导致基因组不稳定。在这里，我们报道了剪接因子 SRSF1 和 FANCD2 物理相互作用并共同作用，通过 mRNA 输出调节抑制 R 环的形成。我们表明 SRSF1 以 RNA 依赖性方式刺激 FANCD2 单泛素化。反过来，FANCD2 单泛素化被证明对 SRSF1-NXF1 核输出复合物和 mRNA 输出的组装至关重要。重要的是，几种 SRSF1 癌症相关突变体无法与 FANCD2 相互作用，导致 FANCD2 单泛素化效率低下、mRNA 输出减少和 R 环积累。我们提出了一个模型，其中 SRSF1 和 FANCD2 相互作用通过调节 mRNA 输出将 DNA 损伤反应与避免致病性 R 环联系起来。

"点击查看英文标题和摘要"

更新日期：2024-01-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南