Cyclins G1 cyclin (cyclin D) S-phase cyclins (cyclins E and A) mitotic cyclins (cyclins B and A)

Cyclin-dependent kinases (Cdks) G1 Cdk (Cdk4)

S-phase Cdk ((Cdk2) M-phase Cdk (Cdk1

Proteins in the CytoplasmAffect Cell Cycle Control

Cyclins cycle!!!

The M Phase Promoting Factor

• Function and Composition

– Composed of Cdk 1 and cyclins A or B– Rises when E cyclin is destroyed

during G2– Assembly of mitotic spindle– Breakdown of nuclear envelope– Condensation of the chromosomes– Phosphorylates histones, nuclear

filaments and microtubule associated proteins that form the spindle

– Promotes the degredation of G2 cyclin (Interesting)

– Homework:– Investigate the function and composition of the

G1 cyclin (cyclin D) and Cdk (Cdk4) as well as the S-phase promoting factor (cyclin E and A and Cdk 2).

Other proteins control the cycle as well----APC (cyclosome)

• Allows sister chromatids to separate by triggering destruction of cohesins

• Destroys cyclin B by ubiquinating it

• Turns on G1 cyclin for the next cycle

• Degrades geminin, a protein which prevents DNA replication

Cell cycle game

• http://nobelprize.org/educational_games/medicine/2001/cellcycle.html

• http://www.bama.ua.edu/~hsmithso/class/bsc_495/spindle/spindle_web.html

Other proteins monitor the cell cycle for lethal mistakes

G0

Checkpoints

                                                                                                G1

checkpoints

1. DNA damage checkpoints

a. G1 checkpoint-Damage inhibits cdk2 until DNA is repaired or cell enters apoptosis

b. G2 checkpoint -Check for completion of DNA synthesis by monitoring Okasaki fragments.

2. Spindle checkpoints

a. check all kinetochores for attachment to spindles.

Checkpoints require proteins.

Guardians of the Genome

• p53-senses DNA damage and halt progression of the cell cycle. It is a tumor supressor gene. Mutations in p53 are recessive. Over 50% of all cancers have mutant p53.

• ATM (ataxia telangiectasia mutated)-detects double stranded breaks in DNA. Maintains telomere length.

• MAD (mitotic arrest deficient)- binds a kinetochore until a spindle connects. If no spindle attaches, entry into anaphase is blocked by inhibiting APC. Mutations in MAD produce aneuploidy.

•