- Updated syllabus online (fills in one omi:ed lecture topic) - Office hours: ANY of the TA office hours Tribeta tutoring : 4th floor lounge of Hitchcock, Monday-Thursday 3:30pm – 6:30pm My office hours (2!) - this room (Kane 120), Thursdays from 12:30 – 1pm - Hitchcock 143, Thursdays from 5-6pm Hannah Chapin, PhD Outline Questions Cell Cycle Regulaon • What are the steps of the cell cycle? – What is the funcVon of each step? – What are the important pieces of cellular machinery involved? • What is a cell cycle checkpoint? • How do cyclins work to regulate progression through the cell cycle? – How to posiVve and negave feedback play roles in this regulaon? Chromosomes • DNA is packaged into chromosomes • Highly condensed DNA • Each daughter cell needs to get one copy of every chromosome (22 pairs, plus 1 pair of sex chromosomes) Cell cycle Metaphase Interphase Prophase Anaphase (Prometaphase) Telophase Cell cycle G1 S and G2 Mitosis Sister chromatids separate; one chromosome copy goes to each daughter nucleus. Sister Kinetochore chromatids Centrioles Centrosomes Chromosomes Early spindle apparatus Polar microtubules Kinetochore microtubules Interphase Prophase Prometaphase Metaphase Cytoplasm is divided. Anaphase Telophase Cell division Cell cycle checkpoints • Why have cell cycle checkpoints? • What is G0? G2 checkpoint Metaphase checkpoint Pass this checkpoint if: Pass this checkpoint if: • chromosomes have • all chromosomes are replicated successfully attached to spindle • DNA is undamaged apparatus • activated MPF is present Mit osis Sec gap gap rst Fi sis G1 checkpoint Pass this checkpoint if: Mature cells do not • cell size is adequate pass this checkpoint • nutrients are sufficient (they enter G0 state) • social signals are present • DNA is undamaged Checkpoint regulaon: MPF • A checkpoint needs to be – EffecVve at affecVng many proteins – Rapidly turned on and off – Easily created – shouldn’t require extensive protein synthesis or modificaon THE M-phase CHECKPOINT G1 S G2 M phase G1 S G2 M phase G1 S Mitosis Promo@nG Factor is made up of: Cyclin, Cdk and Cyclin-bound Phosphate P P P MPF Cdk Concentraon P MPF is ac@vated By the dephosphoryla@on of MPF CDK each cycle Time worksheet DeacVvaon: MPF is deacVvated by an enzyme complex that is acVvated by steps in mitosis. Cyclin is also targeted for degradaon (ubiquiVn-dependent proteasomal degradaon). Key Concepts • Mitosis produces two idencal, somac cells – Chromosomes package DNA – Chromosomes are replicated and divided up between the two new cells (each cell geng one copy of every chromosome) • There are a series of stages that the cell moves through as it divides – G1, S, G2, then M phase, consisVng of prophase, metaphase, anaphase and telophase. – Some cells enter G0 and cease dividing • Checkpoints prevent the cell from dividing before it’s ready, or if it has DNA damage. There are mulVple checkpoints, each with different inputs. • MPF is important for progression through the G2 checkpoint – Made up of Cyclin and Cdk – Phosphorylaon regulates acVvity – both of Cdk and of mitosis-promoVng proteins – PosiVve and negave feedback regulate MPF acVvaon, inacVvaon and degradaon .