REGULATION OF Cdc25A STABILITY AFTER DNA DAMAGE AND ITS ROLE IN CHECKPOINT
PROGRESSION
A. R. Goloudina, 1 N. D. Aksenov, V. A. Pospelov
Institite of Cytology RAS, St. Petersburg, Russia;
1 e-mail: nastena18@mail333.com
Cdc25A phosphatase regulates cell cycle progression by removing the inhibitory phosphates from cyclin-dependent
kinases. Activity of Cdc25A depends on its phosphorylation status. During normal cell cycle progression and after DNA damage
phosphorylation by Chk1 (or Chk2) triggers Cdc25A degradation via ubiquitin-proteasome pathway. In this study we investigate the role
of various phosphorylation sites (Ser123, Ser75, Ser17 and Ser115) in the regulation of Cdc25A stability. We have shown that only
S75A mutation abrogates Cdc25A degradation both in normal and stress conditions. We also studied the influence of stable form of
Cdc25A on checkpoint progression after DNA damage. We have found out that delay in DNA synthesis after UV and IR does not depend
on Cdc25A activity. However, the presence of stable Cdc25A increases the number of mitotic cells after these stresses.
Key words: DNA damage, cell cycle checkpoint, Chkl, Cdc25A, HeLa
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