A phosphorylation-and-ubiquitylation circuitry driving ATR activation and homologous recombination

DSpace/Manakin Repository

A phosphorylation-and-ubiquitylation circuitry driving ATR activation and homologous recombination

Citable link to this page

 

 
Title: A phosphorylation-and-ubiquitylation circuitry driving ATR activation and homologous recombination
Author: Dubois, Jean-Christophe; Yates, Maïlyn; Gaudreau-Lapierre, Antoine; Clément, Geneviève; Cappadocia, Laurent; Gaudreau, Luc; Zou, Lee; Maréchal, Alexandre

Note: Order does not necessarily reflect citation order of authors.

Citation: Dubois, Jean-Christophe, Maïlyn Yates, Antoine Gaudreau-Lapierre, Geneviève Clément, Laurent Cappadocia, Luc Gaudreau, Lee Zou, and Alexandre Maréchal. 2017. “A phosphorylation-and-ubiquitylation circuitry driving ATR activation and homologous recombination.” Nucleic Acids Research 45 (15): 8859-8872. doi:10.1093/nar/gkx571. http://dx.doi.org/10.1093/nar/gkx571.
Full Text & Related Files:
Abstract: Abstract RPA-coated single-stranded DNA (RPA–ssDNA), a nucleoprotein structure induced by DNA damage, promotes ATR activation and homologous recombination (HR). RPA is hyper-phosphorylated and ubiquitylated after DNA damage. The ubiquitylation of RPA by PRP19 and RFWD3 facilitates ATR activation and HR, but how it is stimulated by DNA damage is still unclear. Here, we show that RFWD3 binds RPA constitutively, whereas PRP19 recognizes RPA after DNA damage. The recruitment of PRP19 by RPA depends on PIKK-mediated RPA phosphorylation and a positively charged pocket in PRP19. An RPA32 mutant lacking phosphorylation sites fails to recruit PRP19 and support RPA ubiquitylation. PRP19 mutants unable to bind RPA or lacking ubiquitin ligase activity also fail to support RPA ubiquitylation and HR. These results suggest that RPA phosphorylation enhances the recruitment of PRP19 to RPA–ssDNA and stimulates RPA ubiquitylation through a process requiring both PRP19 and RFWD3, thereby triggering a phosphorylation-ubiquitylation circuitry that promotes ATR activation and HR.
Published Version: doi:10.1093/nar/gkx571
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5587784/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34491914
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters