Cell-cycle and Checkpoint Control

Initial insight of the role of CSN in cell-cycle control came from the finding that csnl and csn2 deletion S. pomhe strains have an S-phase delay [52]. Interestingly, this effect did not occur in strains missing other CSN subunits. The S-phase delay was caused by the accumulation of the cell-cycle inhibitor Spdl (S-phase delayed 1), which is involved in the misregulation of the ribonucleotide reductase (RNR). RNR catalyzes the production of deoxyribonucleotides for DNA synthesis and 

Moreover, the CSN is involved in checkpoint control. The double deletions of csnl and csn2 mutants crossed with checkpoint pathway mutants such as rad3, chk, and cdsl are synthetically lethal in S. pombe [52]. Cdsl kinase is constitutively activated in csnl mutants. Similarly, loss of csn5 in Drosophila results in activation of Mei-41, one of the ATM/ATR family kinases involved in meiotic checkpoint upon DNA damage [90]. 

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Shapiro GI, Harper JW. Anticancer drug targets cell cycle and checkpoint control. J. Clin. Invest. 1999 104 1645-1653. 

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