Cell Cycle &

Cell Cycle Control

6. Cell Cycle and Cell Cycle Control• 6.1 Phases of Cell Cycle• 6.2 Special Apparatus of Mitosis

6.2.1 Chromatin/Chromosome Chromatin DNAPacking of ChromatinNucleosome, histone codes, epigenetic phenomena

6.2.2 Spindle

• 6.3 Cell Cycle Control6.3.1 Core set of cell cycle control system6.3.2 Cell cycle phases are triggered sequentia

lly6.3.3 Check points in cell cycle6.3.4 proto-oncogene and tumor suppressor

gene

6.1 Phases of Cell Cycle6.1.1 Cell cycle

– The cell cycle is process from the end of a cell division to the start of the next cell division. Cell cycle entails an ordered series of macromolecular events that lead to cell division and the production of two daughter cells each containing chromosomes identical to those of the parental cell.

6.1.2 Phases of cell cycle– The primary events of a mammalian cell cycle

are replication of chromosomes and their segregation to daughter cells with extraordinarily high fidelity.

– According to this, cell cycle can be divided into INTERPHASE which includes G1, S, G2 phase and DIVISION which is equal to M phase.

– M phase includes MITOSIS and CYTOKINESIS

– G0 phase: not divides, perform particular functions, can return to the cell cycle when proper be stimulated.

Phase of Cell Cycle

6.2 Special Apparatus of Mitosis6.2.1 Chromatin/Chromosome

– Chromatin DNA p228• There are three kinds of sequence elements in a

chromatin DNA– 1 centromere– 2 telomere– Several replication origins

replication origins at which DNA polymerases and other

proteins initiate synthesis of DNA.centromere attach any chromosome that contains

it to mitotic spindle during M phase and guarantees the proper separation of chromosomes.

telomeres permit a linear chromosome to be co

mpletely replicated.

• Packing of Chromatin– Nucleosome

• octamer of H2A, H2B, H3, H4.• 146bp binding DNA and 0~80bp linker DNA• Linker DNA are bound by H1 histone and are sen

sitive to endonuclease.

(2) 染色体多级螺旋化模型

– histone codes, epigenetic phenomena– Modification of histone influence chromatin structu

re participate in the regulation of transcription.• (1) acetylation and deacetylation Lys-NH2 the gr

eater the acetylation, the less chromatin condensation

• (2) methylation Lys-NH2, Arg a process that pevents acetylation

• (3) phosphorylation Ser and Thr hydroxy introducing a negative charge

– Epigenetic: not depend on DNA sequence

6.2.2 Spindle p310

• 6.3 Cell Cycle Control6.3.1 Core set of cell cycle control system

cyclincyclin dependent kinases, CDKscyclin dependent kinases inhibitors, CKIsanaphase promoting complex, APC

• cyclin A~H– G1 phase cyclin cyclin C,D,E are only synthesized at G1 phase and degr

aded at S phase– S phase cyclin cyclin A are only synthesized at G1 phase and degrade

d at M phase– M phase cyclin cyclin B synthesized at S phase and degraded at the e

nd of M phase• cyclin dependent kinase

• cyclin dependent kinases, CDKs– CDKs 1~8 a kind of protein kinases who will not be fully activated

unless they are binding with cyclins and phosphorylated at proper residues at the same time.

– CDKs are constantly synthesized in the whole cell cycle but are selectively activated by different cyclins and promote the shift of cell cycle phases.

– Table p322, – maturation promoting factor, MPF =CDK1+cyclinB, G2

/M and M phase– START kinase, CDK4/6+cyclinD, G0/G1

• cyclin dependent kinase inhibitors, CKIs– Selectively inhibit the kinase activity of CDKs by bindi

ng to complex of CDKs and cyclins– p21, p27, p16

• anaphase-promoting complex, APC– is a complex of several proteins which is activated duri

ng mitosis to initiate anaphase. – The APC is an E3 ubiquitin ligase that marks target pro

teins, e.g. cyclinB and cyclinA, for degradation by the 26S proteasome. The irreversibility of proteolysis is utilized by cells to give the cell cycle directionality.

Cyclically Activated MPFMitosis Promoting Factor, MPF

Activation of MPF

6.3.3 Checkpoints in cell cycle• Cell cycle checkpoints exist at specific

points in the cell cycle in eukaryotic cells to prevent them from progressing to the next phase of the cell cycle in the event of DNA damage or another condition which would make cell division dangerous for the cell.

• There are 3 main checkpoints which control the cell cycle in eukaryotes.– G1 checkpoint, Restriction point– G2 check point– M check point

6.3.4 proto-oncogenes and tumor suppressor genes• proto-oncogene

– A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer. Proto-oncogenes may play an important role in many essential physiological processes such as cell proliferation, cell death and

• tumor suppressor genes– Tumor suppressor genes are normal

genes that slow down cell division, repair DNA mistakes, and tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don't work properly, cells can grow out of control, which can lead to cancer.