PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.
作者： Alexandre Maréchal , Ju-Mei Li , Xiao Ye Ji , Ching-Shyi Wu , Stephanie A. Yazinski
DOI: 10.1016/J.MOLCEL.2013.11.002
关键词:
摘要: PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although role for well characterized, its DDR remains elusive. Through proteomic screen proteins that interact with RPA-coated single-stranded (RPA-ssDNA), we identified as sensor of damage. directly binds RPA localizes to sites via RPA, promoting ubiquitylation DNA-damage-induced manner. facilitates accumulation ATRIP, regulatory partner ataxia telangiectasia mutated Rad3-related (ATR) kinase, at sites. Depletion compromised phosphorylation ATR substrates, recovery stalled replication forks, progression forks on damaged DNA. Importantly, mutants cannot bind or function an E3 failed support response, revealing drives activation by acting RPA-ssDNA-sensing during DDR.
elsevier.com
sci-hub.se 参考文章(67)
Xiaohong Helena Yang, Lee Zou, Recruitment of ATR‐ATRIP, Rad17, and 9‐1‐1 Complexes to DNA Damage DNA Repair, Part B. ,vol. 409, pp. 118- 131 ,(2006) , 10.1016/S0076-6879(05)09007-5
Karlene A. Cimprich, David Cortez, ATR: an essential regulator of genome integrity Nature Reviews Molecular Cell Biology. ,vol. 9, pp. 616- 627 ,(2008) , 10.1038/NRM2450
Timothy W. Sikorski, Scott B. Ficarro, John Holik, TaeSoo Kim, Oliver J. Rando, Jarrod A. Marto, Stephen Buratowski, Sub1 and RPA Associate with RNA Polymerase II at Different Stages of Transcription Molecular Cell. ,vol. 44, pp. 397- 409 ,(2011) , 10.1016/J.MOLCEL.2011.09.013
Niels Mailand, Simon Bekker-Jensen, Helene Faustrup, Fredrik Melander, Jiri Bartek, Claudia Lukas, Jiri Lukas, RNF8 Ubiquitylates Histones at DNA Double-Strand Breaks and Promotes Assembly of Repair Proteins Cell. ,vol. 131, pp. 887- 900 ,(2007) , 10.1016/J.CELL.2007.09.040
Andrés Aguilera, Tatiana García-Muse, R Loops: From Transcription Byproducts to Threats to Genome Stability Molecular Cell. ,vol. 46, pp. 115- 124 ,(2012) , 10.1016/J.MOLCEL.2012.04.009
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
Bunsyo Shiotani, Hai Dang Nguyen, Pelle Håkansson, Alexandre Maréchal, Alice Tse, Hidetoshi Tahara, Lee Zou, Two Distinct Modes of ATR Activation Orchestrated by Rad17 and Nbs1 Cell Reports. ,vol. 3, pp. 1651- 1662 ,(2013) , 10.1016/J.CELREP.2013.04.018
S. Delacroix, J. M. Wagner, M. Kobayashi, K.-i. Yamamoto, L. M. Karnitz, The Rad9–Hus1–Rad1 (9–1–1) clamp activates checkpoint signaling via TopBP1 Genes & Development. ,vol. 21, pp. 1472- 1477 ,(2007) , 10.1101/GAD.1547007
Vincenzo Costanzo, David Shechter, Patrick J Lupardus, Karlene A Cimprich, Max Gottesman, Jean Gautier, An ATR- and Cdc7-Dependent DNA Damage Checkpoint that Inhibits Initiation of DNA Replication Molecular Cell. ,vol. 11, pp. 203- 213 ,(2003) , 10.1016/S1097-2765(02)00799-2
C. J. David, A. R. Boyne, S. R. Millhouse, J. L. Manley, The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65–Prp19 complex Genes & Development. ,vol. 25, pp. 972- 983 ,(2011) , 10.1101/GAD.2038011