Ago2 facilitates Rad51 recruitment and DNA double-strand break repair by homologous recombination

作者: Min Gao , Wei Wei , Ming-Ming Li , Yong-Sheng Wu , Zhaoqing Ba

DOI: 10.1038/CR.2014.36

关键词:

摘要: DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We others have previously shown that class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs associated with Argonaute (Ago) proteins play an important role in repair, though the mechanism through which they act remains unclear. Here, we report diRNAs repair restricted by homologous recombination (HR) it specifically relies on effector protein Ago2 mammalian cells. Interestingly, show forms complex Rad51 interaction enhanced cells treated ionizing radiation. demonstrate accumulation at sites HR depend catalytic activity RNA-binding capability Ago2. In contrast, resection as well RPA Mre11 loading unaffected or Dicer depletion, suggesting very likely functions directly mediating DSBs. Taken together, our findings suggest guided diRNAs, can promote recruitment and/or retention DSBs facilitate HR.

参考文章(31)
Longhou Fang, YiGuo Wang, Dan Du, Guang Yang, Tim Tak Kwok, Siu Kai Kong, Benjamin Chen, David J Chen, Zhengjun Chen, Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair Cell Research. ,vol. 17, pp. 100- 116 ,(2007) , 10.1038/SJ.CR.7310145
Alessandro A. Sartori, Claudia Lukas, Julia Coates, Martin Mistrik, Shuang Fu, Jiri Bartek, Richard Baer, Jiri Lukas, Stephen P. Jackson, Human CtIP promotes DNA end resection Nature. ,vol. 450, pp. 509- 514 ,(2007) , 10.1038/NATURE06337
Jin-Biao Ma, Keqiong Ye, Dinshaw J. Patel, Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature. ,vol. 429, pp. 318- 322 ,(2004) , 10.1038/NATURE02519
Eleni P. Mimitou, Lorraine S. Symington, Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing Nature. ,vol. 455, pp. 770- 774 ,(2008) , 10.1038/NATURE07312
Damien D'Amours, Stephen P. Jackson, The Mre11 complex: at the crossroads of dna repair and checkpoint signalling. Nature Reviews Molecular Cell Biology. ,vol. 3, pp. 317- 327 ,(2002) , 10.1038/NRM805
Jiri Lukas, Claudia Lukas, Jiri Bartek, More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance Nature Cell Biology. ,vol. 13, pp. 1161- 1169 ,(2011) , 10.1038/NCB2344
Sofia Francia, Flavia Michelini, Alka Saxena, Dave Tang, Michiel de Hoon, Viviana Anelli, Marina Mione, Piero Carninci, Fabrizio d’Adda di Fagagna, Site-specific DICER and DROSHA RNA products control the DNA-damage response Nature. ,vol. 488, pp. 231- 235 ,(2012) , 10.1038/NATURE11179
Bing Xia, Qing Sheng, Koji Nakanishi, Akihiro Ohashi, Jianmin Wu, Nicole Christ, Xinggang Liu, Maria Jasin, Fergus J. Couch, David M. Livingston, Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2 Molecular Cell. ,vol. 22, pp. 719- 729 ,(2006) , 10.1016/J.MOLCEL.2006.05.022
S. Gravel, J. R. Chapman, C. Magill, S. P. Jackson, DNA helicases Sgs1 and BLM promote DNA double-strand break resection Genes & Development. ,vol. 22, pp. 2767- 2772 ,(2008) , 10.1101/GAD.503108
Gyorgy Hutvagner, Juanita McLachlan, Amy E Pasquinelli, Éva Bálint, Thomas Tuschl, Phillip D Zamore, A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA Science. ,vol. 293, pp. 834- 838 ,(2001) , 10.1126/SCIENCE.1062961