CELL CYCLE Flashcards
WHAT ARE THE TWO CONTROL FACTORS OF THE CELL CYCLE
- ASSOCIATION OF CYCLINS WITH CDKS
2. MECHANISMS TO STOP THE CELL CYCLE IF THERE ARE PROBLEMS IE CHECKPOINTS
WHAT DECISIONS CAN A CELL TAKE
QUIESCENT, PROLIFERATE, DIFFERENTIATE
WHAT HAPPENS IN G1
THE CELL GROWS IN PREPARATION FOR DNA REPLICATION AND CERTAIN INTRACELLULAR COMPONENTS UNDERGO REPLICATION
WHAT HAPPENS IN S PHASE
THIS IS WHERE DNA IS REPLICATED
WHAT HAPPENS IN G2
RAPID CELL GROWTH AND PROTEIN SYNTHESIS
WHY DO CYCLINS DECREASE THROUGHOUT THE CYCLE
TO ENSURE THE PROCESS IS UNIDIRECTIONAL
WHY ARE D CYCLINS DIFFERENT
D CYCLINS ARE CONTROLLED BY EXTRACELLULAR SIGNALS - INTEGRINS AND ECM ATTACHMENTS
UP UNTIL WHICH POINT IS THE CELL UNDER EC CONTROL
R POINT. AFTER R POINT THIS IS A CELL AUTONOMOUS PROCESS. CYCLINS AND CDKS FORM COMPLEXES THAT ACTIVATE THE SUBSEQUENT PHASE AND INHIBIT THE PREVIOUS.
HOW ARE CYCLINS AND CDKS REGULATED
CDK INHIBITORS
WHAT INHIBITS CYCLIN D AND ITS CDK4/6 COMPLEXES
CKI SUCH AS P16INK4A/P15INK4B/P18INK4C/P19INK4D
WHAT INHIBITS ALL CYCLINS AND THEIR COMPLEXES APART FROM D
CKI SUCH AS P57KIP2/P27KIP1/P21CIP1
HOW DO CYCLINS DRIVE THE CELL CYCLE
Cyclins drive the events of the cell cycle by partnering with a family of enzymes called the cyclin-dependent kinases (Cdks). A lone Cdk is inactive, but the binding of a cyclin activates it, making it a functional enzyme and allowing it to modify target proteins.
CYCLIN CDK COMPLEXES AT WHICH STAGES
G1: CDK4 and CDK6 depend on the association with cyclin Ds (D1,D2 &D3 = D-type cyclins)
After the R point: E-type cyclins associate with CDK2 phosphorylation of substrates required for entry in S phase
S phase: A-type cyclins replace E cyclins in complex with CDK2 - S phase progression. Later in S-phase, A-type cyclins associate with CDK1
G2: B-type cyclins replace A-type ones in the complex with CDK1
M phase: B-type cyclins/CDK1 - mitosis triggering
G0 to G1: mediated by cyclin C/CDK3 complex
WHAT IS THE RESTRICTION POINT FOR
- IS THE CELL BIG ENOUGH
- IS THE ENVIRONMENT FAVOURABLE
- IS THERE ANY DNA DAMAGE
WHAT IS G2 CHECKPOINT FOR
- IS ALL DNA REPLICATED
- IS THE CELL BIG ENOUGH
- IS THE ENVIRONMENT FAVOURABLE
WHAT IS THE METAPHASE CHECKPOINT FOR
ARE THE CHROMOSOMES ALIGNED ON THE SPINDLE
HOW DOES THE RESTRICTION CHECKPOINT OCCUR
- CYCLIN D AND CDK4/6 FORM A COMPLEX IN G1
- THIS COMPLEX ALLOWS PHOSPHORYLATION OF PRB (THAT IS BOUND TO E2F)
- PHOSPHORYLATION OF PRB INACTIVATES THE PROTIEIN THEREBY FREEING E2F TO BE TRANSCIBED
- TRANSCIPTION OF E2F PRODUCES CYCLIN E AND CDK2 ALLOWING PROGRESSION TO S PHASE
E2F REGULATIONS EXPRESSION OF CDK2 , CYCLIN E AND A
IF THERE IS SIGNICANT DNA DAMAGE P53 STIMULATES PRODUCTION OF P21
P21 INHIBITS ALL CDK COMPLEXES WHICH CAUSES ARREST OF THE CELL CYCLE
TUMOUR SUPPRESSOR RETINBOBLASTOMA PROTEIN INHIBITS E2F EXPRESSION
CYCLIN D AND ITS CDK4/6 COMPLEXES PHOSPHORYLATE PRB WHICH LEADS TO ITsINACTIVATION LEADING TO EXPRESSION OF E2F
E2F CAUSES EXPRESSION OF CYCLIN E AND CDK2 THEREBY S PHASE CAN CONTINUE
WHAT HAPPENS UPON DETECTION OF DNA DAMAGE
- ATM/ATR ASSOCIATES WITH SITE OF DAMAGE
- THIS ACTIVATES KINASES SUCH AS CHK1//CHK2
- THIS CAUSES PHOSPHORYLATION OF P53
- P53 CAN CAUSE P21 GENE TO ACTIVATE ENCODING CYCLIN DEPENDENT KINASE INHIBITORS THEREBY ARRESTING THE CELL CYCLE
WHAT ARE THE CHOICES OF A DAMAGED CELL AND HOW CAN THIS CHANGE
A DAMAGED CELL CAN ARREST UNTIL DAMAGE IS REPAIRED, IF IN G1 IT CAN REVERT TO G0 OR IT CAN TRIGGER APOPTOSIS. THE BALANCE BETWEEN REPAIR AND APOPTOSIS CAN CHANGE OVER TIME.
WHAT ACCOMPANIES FORMATION OF MOST TYPES OF CANCER CELLS
DEREGULATION OF RESTRICTION POINT DECISION MAKING MACHINERY
WHAT IS THE IMPORTANCE OF S PHASE
- DNA MUST BE REPLICATED ACCURATELY
2. DNA MUST BE COPIED ONCE
WHAT IS LICENCING
IN G1 INACTIVE HELICASES ARE LOADED ONTO REPLICATION ORIGINS TO FORM A PRE RC WHICH ARE ACTIVATED IN S PHASE BY S PHASE CDKS
IS THE CELL CYCLE ALWAYS THE SAME
NO, DIFFERENT CELL TYPES IE ESC AND FIBROBLASTS HAVE DIFFERENT CYCLIN PROFILES THAT ARE NOT FULLY UNDERSTOOD.
