Events of The Cell Division Cycle Occur in a Particular Order

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Presentation transcript:

Events of The Cell Division Cycle Occur in a Particular Order

Entering Mitosis Before the Completion of S phase is Bad for Chromosomes and Therefore Bad for Cells

Cell Cycle Checkpoints G1 Elledge, Science 274:1664 (1996)

Substrate-Product versus Extrinsic Control Mechanisms Weinert and Hartwell, Science 246:629 (1989)

Caffeine Abrogates the Replication Checkpoint Molecular Biology of the Cell © 1994 by Bruce Alberts et al

rad9 is the First Cell Cycle Checkpoint Mutant 0 hrs at res temp 3 hrs at res temp cdc9 (DNA ligase) cdc9 rad9 Weinert and Hartwell, Science 246:629 (1989)

Cell Cycle Checkpoints Improve Cell Viability Weinert and Hartwell, Science 246:629 (1989)

Cell Cycle Checkpoints G1 Why always negative regulation?

A Mechanism Involving Negative Regulation is More Robust Very different situations Anaphase: Not very different situations Anaphase: GO x 5 GO x 6

How do Cell Cycle Checkpoints Work? G1

How do Cell Cycle Checkpoints Work? Zhou and Elledge Nature 408, 433 - 439 (2000)

Replication and Damage Checkpoints in Yeast Elledge, Science 274:1664 (1996)

Inhibitory CDC2 Phosphorylation is a kinase is a phosphatase

G2 Arrest Induced by DNA Damage Signal Sensor Transducer Effector Cytoplasm Nucleus

Metaphase in a mammalian cell

The Metaphase to Anaphase Transition (also called the cyclosome NOT the tumor suppressor!!)

The Spindle Assembly Checkpoint

The Spindle Assembly Checkpoint Mitotic Checkpoint Complex (MCC) Mad2 BubR1 Bub3 CDC20 Bub1

Mitotic Defects Leading to Aneuploidy Weaver BA, Cleveland DW. Does aneuploidy cause cancer? Curr Opin Cell Biol. 2006 Dec;18(6):658-667.

Spindle Assembly Checkpoint Genes that are Mutated and/or Misregulated in Human Cancers Weaver BA, Cleveland DW. Does aneuploidy cause cancer? Curr Opin Cell Biol. 2006 Dec;18(6):658-667.

Chi and Jeung, J. Cell. Biochem. 102:531 (2007)