Nutrient Limitation Inactivates Mrc1-to-Cds1 Checkpoint Signalling in Schizosaccharomyces pombe

Cells
Jessica FletcherThomas Caspari

Abstract

TheS. pombecheckpoint kinase, Cds1, protects the integrity of stalled DNA replication forks after its phosphorylation at threonine-11 by Rad3 (ATR). Modified Cds1 associates through its N-terminal forkhead-associated domain (FHA)-domain with Mrc1 (Claspin) at stalled forks. We report here that nutrient starvation results in post-translational changes to Cds1 and the loss of Mrc1. A drop in glucose after a down-shift from 3% to 0.1-0.3%, or when cells enter the stationary phase, triggers a sharp decline in Mrc1 and the accumulation of insoluble Cds1. Before this transition, Cds1 is transiently activated and phosphorylated by Rad3 when glucose levels fall. Because this coincides with the phosphorylation of histone 2AX at S129 by Rad3, an event that occurs towards the end of every unperturbed S phase, we suggest that a glucose limitation promotes the exit from the S phase. Since nitrogen starvation also depletes Mrc1 while Cds1 is post-translationally modified, we suggest that nutrient limitation is the general signal that promotes exit from S phase before it inactivates the Mrc1-Cds1 signalling component. Why Cds1 accumulates in resting cells while its activator Mrc1 declines is, as yet, unclear but suggests a novel function of C...Continue Reading

References

May 28, 1973·Molecular & General Genetics : MGG·R Egel
May 23, 1998·Science·M N BoddyP Russell
May 18, 1999·Molecular and Cellular Biology·J M BrondelloP Russell
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·G W Brown, T J Kelly
Sep 9, 2000·FEMS Microbiology Reviews·C L FloresC Gancedo
Nov 14, 2000·Molecular and Cellular Biology·M N BoddyP Russell
Nov 21, 2001·Nature Cell Biology·K Tanaka, P Russell
Nov 5, 2002·Journal of Cell Science·Holly CapassoNancy C Walworth
Aug 10, 1956·Science·O WARBURG
Dec 24, 2005·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Satoru Mochida, Mitsuhiro Yanagida
Jun 24, 2006·Methods in Enzymology·Mihoko KaiTeresa S-F Wang
Mar 14, 2007·Cell·Jue D WangAlan D Grossman
Jun 11, 2010·Chemistry & Biology·Yves PommierChristophe Marchand
Aug 24, 2010·The Journal of Biological Chemistry·Xin ZhouTakayoshi Kuno
Aug 23, 2012·Nature Communications·Yoshitaka NakayamaHidetoshi Iida
Feb 13, 2013·BMC Microbiology·Marisa MadridJosé Cansado
Nov 7, 2013·G3 : Genes - Genomes - Genetics·Nadia Graciele KrohnGustavo Henrique Goldman
Nov 30, 2013·Nature Reviews. Drug Discovery·Chiara GorriniTak W Mak
Aug 8, 2014·Redox Biology·Stanley AndrisseJonathan S Fisher
Sep 8, 2015·Cell Reports·Kobi J Simpson-LavyMark Johnston
Jan 19, 2016·Trends in Biochemical Sciences·Maria V Liberti, Jason W Locasale

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.