Accession Number:

ADA359281

Title:

Role of the Cdk Inhibitor Sic 1 in Start

Descriptive Note:

Annual rept. 1 Aug 1997-31 Jul 1998

Corporate Author:

COLD SPRING HARBOR LAB OF QUANTITATIVE BIOLOGY NY

Personal Author(s):

Report Date:

1998-08-01

Pagination or Media Count:

18.0

Abstract:

Mpst cells have four fundamental goals they must replicate their DNA, segregate their chromosomes, double their mass, and divide. Coordination of these events is essential. I have used the budding yeast S. cerevisiae to dissect the molecular events that control cell cycle progression. I have shown that not only are G1 cyclin-CDK complexes highly unstable rate-limiting activators for cell cycle progression, but that their essential function is to regulate the initiation of DNA replication by phosphorylating and promoting the degradation of a key cell cycle inhibitor, Sic1 1,2. In fact, cyclin-CDK-regulated proteolysis may constitute the major mechanism of cell cycle control 3. Moreover, Sic1 appears to be the analog of the RB tumor suppressor gene. I have shown that Sic1, like RB, controls the timing of S-phase, ensures genomic stability, and most significantly, sic1 deletions, like rb deletions, completely remove cell cycle dependence on G1 cyclins 1,22. Furthermore, Sic1 protein levels may set the G1 cyclin threshold for cell cycle progression. Ongoing research focuses on two questions 1 How does Sic1 or other key substrates control cell cycle progression and 2 What mechanism couples and coordinates cell growth with cell cycle progression

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE