1. MOLECULAR CELL BIOLOGY
SIXTH EDITION
CHAPTER 20
Regulating the Eukaryotic
Cell Cycle
Copyright 2008 © W. H. Freeman and Company

2. V. Replication at Each Origin is Initiated Only Once
during the Cell Cycle
*1 Multiple replication origin
*2 Only once initiation
Yeast Replication origin
a. 11-base-pair conserved core sequence
b. Origin recognition complex (ORC)
c. Initiation factors
d. Prereplicatiom complex
Regulation of prereplication complexs
a. Phosphorylated initiation factor
b. S-phase cyclin-CDK and DDK
c. B-type cyclin-CDK
d. Cdc14

3. 20.6 Cell-Cycle Control in Mammalian Cells
Extracellular signal
Signal transduction
Intracellular cues
I. Mammalian Restriction Point
Growth factors (mitogen)
Restriction point
II. Mammalian CDKs and Cyclins
Cyclin-dependent kinase (CDK)
a. 적어도 4개가 확인
b. 각 phase마다 작동하는 CDKs가 다름:
* G1; CDK4, 6
* mid G1 to S; CDK2
* G2 to M; CDK1

4. (2) Cyclins ( Two major group : G1 cyclins & B type )
a. Ability to complement yeast mutant로 확인
b. Mid- G1 : D
c. Late- G1 : E
d. S-phase : A
e. Mitotic : B, A
f. Destruction box
(3) Cyclin D is essential for passage
a. Anti-Cyclin D Ab microinjection
b. Before 14 h
c. After 14h
(4) G0 cells

5. III. Regulated Expression of Two Classes of Genes
Return G0 mammalian cells to the cell cycle
Early-response genes
a. Activation of preexisting TF
b. Induction of gene expression : c-Jun, C-Fos
(2) Delayed-response genes
a. Early gene product 에 의한 gene expression이 조절됨
b. Mid-G1 cyclin, Late-G1 cyclins , CDKs, E2F factors
c. Growth factor를 restriction point passage 직전에 제거 시
d. Cyclin D mRNA의 translation 조절
IV. Passage though the Restriction Point
(1) E2F factors : Activation of cyclin E, A expression
(2) RB protein : Tumor-suppressor
(3) Regulation of Rb and E2F activity

6. V. Cyclin A: for DNA synthesis CDK1: for Mitosis Entry
(1) Cyclin A-CDK2 complex (S-phase complex)
(2) CDK inhibitory proteins (CKIs): p27KIP1, p57KIP2, p21CIP
a. Sic1과 기능이 유사
b. p27KIP1
(3) Cyclin-CDK2 function의 조절( MPF 와 유사)
a. Cdc25A phosphtase
b. G1 to S transition
c. Activation in late G1
(4) Initiation of DNA replication
a. Phosphorylation of preinitiation complex : IFs
b. Geminin
c. Cdc14 phosphatase

7. VI. Two Types of Cyclin-CDK inhibitors
(5) CDK1: G2 & Mitosis에서 주된 역할
a. Cyclin A & B 와 association
b. Cdc25C Phosphatase
(6) Cyclin B
a. Synthesis
b. Cyclin B shuttles between the cytosol and nucleus
c. Removal by APC/C-Cdh1
VI. Two Types of Cyclin-CDK inhibitors
CKI type : S- phase 로 entry전에 제거
a. Inhibition of CDK2
b. p21CIP : DNA Damage 시 작동
c. p27KIP1 knockouts
d. p57KIP2 knockouts
INK4 type
a. Binding to CDK4 & CDK6
b. Tumor suppressor

8. 20.7 Checkpoints in Cell-Cycle Regulation
*1 Fundamental processes in the eukaryotic cell cycle
DNA prereplication complexs assemble at origin
G1 cyclin-CDK inactivate Cdh1
G1 C-C activates expression of S-phase C-C component
G1 C-C phosphorylates S-phase inhibitor
SCF/proteasome degrades phosphorylated S-phase C-C inhibitor
S cyclin-CDK activates prereplication complex
Cdc25 phosphatase activates Mitotic cyclin-CDKs
APC/C-Cdc20 degrade securin
Cdc14 phosphatase activates Cdh1

9. *2 Checkpoints in Cell-Cycle Regulation
Intra S phase checkpoint : Inhibition of Cdc25C
Spindle-assembly checkpoint : Inhibition of Cdc20
Spindle-position checkpoint : Prevention of Cdc14
DNA-damage checkpoint : Inhibition of Cdc25A
I . Intra S phase checkpoint
Association of ATR with replication fork
Chk1 kinase
Cdc25 phosphatase
Checkpoint controller
II. Spindle-assembly checkpoint
Mad2 (Mitotic arrest defective 2)
p31comet

10. III. Proper Segregation checkpoint
The spindle-position checkpoint
(2) Mitotic exit network
a. Tem1 : GTPase superfamily
b. Releasing of Cdc14
(3) Checkpoint인 이유
a. Telophase initiation
b. Kin4 kinase

11. IV. DNA-damage checkpoint
a. Chemical agents
b. Irradiation
c. G1 arrest or G2 arrest
(2) Tumor-suppressor gene products, ATM & Chk2
ATM or Chk2 mutation
Encode protein kinase
Inactivation of Cdc25A
(3) p53 protein (Tumor-suppressor)
DNA damage
Transcription factor
Degradation by Mdm2
ATM & ATR
Activation of p21CIP
p53 induced apoptosis

12. I. Key Features Distinguish Meiosis from Mitosis
Comparison of mitosis and meiosis
Chiasmata
II. Repression of G1 Cyclins and a Meiosis-specific
Protein Kinase Promote Premeiotic S phase
S. cerevisiae and S. pombe 의 meiosis
Nitrogen and Carbon source 부족 시
Ime2 의 Induction
Meiosis I 과 II 사이에 DNA replication의 suppression
MPF activity
2nd rise in MPF activity
Cdc20 activity is increased
Separase is activated

13. III. Two Physical links: Recombination
Meiosis-specific cohesin subunit
Homologous chromosome사이에 physical links
Recombination
Cohesin function during mitosis and meiosis
Meiotic chromosome 와 cohesin
IV. Rec 8 Stability
Meiosis I
Meiosis II

14. V. The Monopolin Complex Co-orient Sister Kinetochores in Meiosis I
(1) MAMI
(2) Monopolin complex
VI. Tension on Spindle Microtubles Contributes to Proper Spindle Attachment
(1) Mitosis 에서
(2) Meiosis I 에서