Dullovi Arlinda, Ozgencil Meryem, Rajvee Vinothini, Tse Wai Yiu, Cutillas Pedro R, Martin Sarah A, Hořejší Zuzana
Centre for Cancer Cell & Molecular Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Mass Spectrometry Laboratory, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
iScience. 2023 Feb 1;26(3):106107. doi: 10.1016/j.isci.2023.106107. eCollection 2023 Mar 17.
The DNA-damage response is a complex signaling network that guards genomic integrity. The microtubule cytoskeleton is involved in the repair of DNA double-strand breaks; however, little is known about which cytoskeleton-related proteins are involved in DNA repair and how. Using quantitative proteomics, we discovered that microtubule associated proteins MAP7 and MAP7D1 interact with several DNA repair proteins including DNA double-strand break repair proteins RAD50, BRCA1 and 53BP1. We observed that downregulation of MAP7 and MAP7D1 leads to increased phosphorylation of p53 after γ-irradiation. Moreover, we determined that the downregulation of MAP7D1 leads to a strong G1 arrest and that the downregulation of MAP7 and MAP7D1 in G1 arrested cells negatively affects DNA repair, recruitment of RAD50 to chromatin and localization of 53BP1 to the sites of damage. These findings describe for the first time a novel function of MAP7 and MAP7D1 in cell cycle regulation and repair of DNA double-strand breaks.
DNA损伤反应是一个保护基因组完整性的复杂信号网络。微管细胞骨架参与DNA双链断裂的修复；然而，对于哪些细胞骨架相关蛋白参与DNA修复以及如何参与，我们知之甚少。通过定量蛋白质组学，我们发现微管相关蛋白MAP7和MAP7D1与几种DNA修复蛋白相互作用，包括DNA双链断裂修复蛋白RAD50、BRCA1和53BP1。我们观察到，MAP7和MAP7D1的下调导致γ射线照射后p53磷酸化增加。此外，我们确定MAP7D1的下调导致强烈的G1期阻滞，并且G1期阻滞细胞中MAP7和MAP7D1的下调对DNA修复、RAD50募集到染色质以及53BP1定位到损伤位点产生负面影响。这些发现首次描述了MAP7和MAP7D1在细胞周期调控和DNA双链断裂修复中的新功能。
