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Plos Genetics : Sensing of Replication Stress and Mec1 Activation Act Through Two Independent Pathways Involving the 9-1-1 Complex and Dna Polymerase Ε, Volume 7

By Copenhaver, Gregory P.

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Book Id: WPLBN0003931841
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Sensing of Replication Stress and Mec1 Activation Act Through Two Independent Pathways Involving the 9-1-1 Complex and Dna Polymerase Ε, Volume 7  
Author: Copenhaver, Gregory P.
Volume: Volume 7
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Historic
Publication Date:
Publisher: Plos

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Copenhaver, G. P. (n.d.). Plos Genetics : Sensing of Replication Stress and Mec1 Activation Act Through Two Independent Pathways Involving the 9-1-1 Complex and Dna Polymerase Ε, Volume 7. Retrieved from http://www.ebooklibrary.org/


Description
Description : Following DNA damage or replication stress, budding yeast cells activate the Rad53 checkpoint kinase, promoting genome stability in these challenging conditions. The DNA damage and replication checkpoint pathways are partially overlapping, sharing several factors, but are also differentiated at various levels. The upstream kinase Mec1 is required to activate both signaling cascades together with the 9-1-1 PCNA-like complex and the Dpb11 (hTopBP1) protein. After DNA damage, Dpb11 is also needed to recruit the adaptor protein Rad9 (h53BP1). Here we analyzed the mechanisms leading to Mec1 activation in vivo after DNA damage and replication stress. We found that a ddc1Ddpb11-1 double mutant strain displays a synthetic defect in Rad53 and H2A phosphorylation and is extremely sensitive to hydroxyurea (HU), indicating that Dpb11 and the 9-1-1 complex independently promote Mec1 activation. A similar phenotype is observed when both the 9-1-1 complex and the Dpb4 nonessential subunit of DNA polymerase e (Pole) are contemporarily absent, indicating that checkpoint activation in response to replication stress is achieved through two independent pathways, requiring the 9-1-1 complex and Pole.

 

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