News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  27th October 2009  
 

DNA Damage Checkpoint Maintains Cdh1 in an Active State to Inhibit Anaphase Progression

 
 




Author
Tao Zhang1, 2, Saurabh Nirantar1, 2, Hong Hwa Lim1, Indrajit Sinha1 and Uttam Surana1

Abstract
DNA damage checkpoint prevents segregation of damaged chromosomes by imposing cell-cycle arrest. In budding yeast, Mec1, Chk1, and Rad53 (homologous to human ATM/ATR, Chk1, and Chk2 kinases, respectively) are among the main effectors of this pathway. The DNA damage checkpoint is thought to inhibit chromosome segregation by preventing separase-mediated cleavage of cohesins. Here, we describe a regulatory network that prevents segregation of damaged chromosomes by restricting spindle elongation and acts in parallel with inhibition of cohesin cleavage. This control circuit involves Rad53, polo kinase, the anaphase-promoting complex activator Cdh1, and the bimC kinesin family proteins Cin8 and Kip1. The inhibition of polo kinase by Rad53-dependent phosphorylation prevents it from inactivating Cdh1. As a result, Cdh1 remains in a partially active state and limits Cin8 and Kip1 accumulation, thereby restraining spindle elongation. Hence, the DNA damage checkpoint suppresses both cohesin cleavage and spindle elongation to preserve chromosome stability.

 

 
 

 
 


Figure Legend: A: Forced cohesin cleavage in DNA-damaged cells fails to trigger anaphase B. G1 synchronized cdc13-1 TEV and cdc23-1 TEV cells were released into YEP+raff medium at 32oC for 3.5 h. Galactose was added to one half of the culture to induce TEV protease while glucose was added to the other half and the incubation was continued at 32oC. B: Cdc5 phosphorylation in DNA damaged cells. G1 synchronized cdc13-1 CDC5-HA3, GAL-PDS1 CDC5-HA3, and cdc13-1 rad53-21 CDC5-HA3 cells were released into YEP+raff+gal medium at 32oC for 3 h. Whole cell extracts were subjected to 2D gel electrophoresis. In a parallel experiment, G1 synchronized cdc13-1 CDC5-HA3 and cdc28-1N CDC5-HA3 cells were released into YEPD medium at 37oC for 3 h and samples were subjected to 2D gel electrophoresis. C: A regulatory scheme by which DNA damage checkpoint prevents progression through mitosis.

Published in Developmental Cell, Volume 17, Issue 4, 541-551, 20 October 2009

For more information on Uttam SURANA’s Lab, Please Click here.