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3P 1-1
From chromosome to chromatin to solenoid to DNA
Chromosomes
3P3-2
5
O
4
1
3
2
5
3P3-2
3
4F4-4
3F2-10
4F4-3
3F8-30
Tangle of
chromatin
spilling
out of lysed
nucleus
2 linked copies of
a chromosome
during mitosis
4F4-21
Central Dogma
Transcription
Transcription
Gene (DNA)
Reverse Transcription
Translation
mRNA
Protein
exons
5’ UTR
3’ UTR
Gene
27Kbp
JUNK???
Gene
27Kbp
300Kbp
300Kbp
Ex1
Intron1
Ex2
145bp
2500bp
145bp
Intron2
2500bp
Template, 3’
New, 5’
3’
DNA Synthesis
5’
4F5-3
4F5-5
CELL CYCLE: Gap1, Synthesis, Gap2, Mitosis ….
H
NH3+
O
C
C
R1
Peptide bond
NH
O
C
C
R2
H
R2
H
R1
NH
O
C
C
R3
R2
H
NH
O
C
C
R4
R1
O --
CRAMBIN: N = 46
TTCCPSIVARSNFNVCRLPGTPEALCATYTGCIIIPGATCPGDYAN
4F6-8
3F3-19
4F6-9
4F6-6
TATA
G9.17
Transcription Start Site
4F6-19
The Gene Network of E.Coli: (bacterium, single cell) (U. Alon)
1.
M.Milyevsky,Y.Tabach, ….T.Pilpel,V. Rotter – in vitro
2.
C. Rosty,M. Sheffer, D.Tsafrir….in vivo, cervical cancer
CDK2
NFY
RB
CDKN2A (p16)
CDK4
E2F
ELK1
CDK6
CHR
CDKN1A (p21)
NFY
p53
Inactivation by
E7 binding
Expression 1-99%
212186_at
220668_s_at
202532_s_at
218115_at
203228_at
206074_s_at
204826_at
203967_at
211814_s_at
212022_s_at
218308_at
202240_at
218755_at
202954_at
202338_at
202095_s_at
203755_at
209644_x_at
202735_at
209773_s_at
210559_s_at
204825_at
204092_s_at
218883_s_at
209172_s_at
207039_at
217733_s_at
201890_at
204170_s_at
218741_at
218782_s_at
204709_s_at
205235_s_at
201202_at
201088_at
211725_s_at
208808_s_at
204146_at
219493_at
217851_s_at
218237_s_at
S19-1noo
S28-1noo
S07-1noo
S35-1noo
S02-1noo
S29-3a6g
S26-2a8+
S20-2e8g
S03-1e8g
S34-2e8g
S23-1a8g
S13-1a8b
S31-3a6g
S08-1e6g
S23-2a8g
S10-1e6b
S18-1e8b
S04-1a8b
S12-1e8b
S05-1a8b
S11-1e3b
S25-3a6g
S22-1e6g
S27-1e6b
S32-2e6g
S17-3a6o
S33-1e6b
S15-2e6g
S09-1e6b
S18-2e8b
S06-1e6+
S14-1e6b
S33-2e6b
S15-1e6g
S21-2a8o
S24-1e6b
S01-1e6g
S14-3e6b
S30-2e8b
C01-3c8o
S16-1e9o
C06-3c8o
C07-3c6o
C03-3c6o
C05-3c8o
CDE / E2F
Degradation
Induced by E6
Mitogens
MAPK
ELK 1
Cervical cancer induced by HPV: two viral oncoproteins (E6,E7) are inserted in DNA
and expressed. They inactivate p53 and Rb and induce proliferation
4F6-21
3 READING FRAMES
VHLTP(EEKSAVTALW){GK}
VN(VDEVGGEALGRLLVV)Y
PWTQRF)F(ESF)GDLST (
PDAVM){G}N (
PKVKAHGKKVLGAFSDGL) (
AH}(LDNLKGTFATLSELHCD) {
KL}HVD{P} {
ENFRLLGNVLVCVLAHHFGKE)FT (
PPVQAAYQKVVAGVANALA) (
HK}YH{
3FtRNA
6-8,9
4F6-65
3FtRNA
4F6-58
4F6-60
3F6-28,29
Central Dogma
Transcription
Gene (DNA)
Translation
mRNA
Protein
Cells express different subset of the genes
In different tissues and under different conditions