P1-1 Cell diagram

3P 1-1

From chromosome to chromatin to solenoid to DNA

P3-2 Chromosome to DNA

3P3-2

Chromosomes

P3-2 Backbone chemistry

3P3-2

1

23

4

5 O

5

3

4F4-4

3F2-10 4F4-3

3F8-30

4F4-21

2 linked copies ofa chromosome during mitosis

Tangle ofchromatin spilling

out of lysed nucleus

Central Dogma

Transcription

mRNAGene (DNA)

Translation

Protein

Transcription

Reverse Transcription

exons

27Kbp 27Kbp300Kbp 300Kbp

Gene Gene

Ex1 Ex2Intron1 Intron2

145bp 145bp2500bp 2500bp

5’ UTR 3’ UTR

JUNK???

3-12,13 DNA replication

4F5-5

DNA Synthesis

Template, 3’

5’

New, 5’

3’

4F5-3

CELL CYCLE: Gap1, Synthesis, Gap2, Mitosis ….

proteins- chain of AA

O --

C

NH3+

H C

R1

O

C

NH

H C

R2

O

C

NH

H C

R3

O

C

NH

H C

R4

O

R1

R2

R1

R2

Peptide bond

CRAMBIN: N = 46TTCCPSIVARSNFNVCRLPGTPEALCATYTGCIIIPGATCPGDYAN

Peptide bond,crambin

4F6-8

4F6-93F3-19

4F6-6

TATA Transcription Start Site

G9.17

4F6-19

The Gene Network of E.Coli: (bacterium, single cell) (U. Alon)

p53

CD

E /

E2F

CH

RE

LK

1

NF

Y

CDK4

CDK6

CDKN1A (p21)

E2F

RB

NFY

CDKN2A (p16)

Mitogens MAPK ELK 1

1. M.Milyevsky,Y.Tabach, ….T.Pilpel,V. Rotter – in vitro

2. C. Rosty,M. Sheffer, D.Tsafrir….in vivo, cervical cancer

CDK2

Cervical cancer induced by HPV: two viral oncoproteins (E6,E7) are inserted in DNAand expressed. They inactivate p53 and Rb and induce proliferation

Inactivation byE7 binding

DegradationInduced by E6

Expression 1-99%

S19-1nooS28-1nooS07-1nooS35-1nooS02-1nooS29-3a6gS26-2a8+S20-2e8gS03-1e8gS34-2e8gS23-1a8gS13-1a8bS31-3a6gS08-1e6gS23-2a8gS10-1e6bS18-1e8bS04-1a8bS12-1e8bS05-1a8bS11-1e3bS25-3a6gS22-1e6gS27-1e6bS32-2e6gS17-3a6oS33-1e6bS15-2e6gS09-1e6bS18-2e8bS06-1e6+S14-1e6bS33-2e6bS15-1e6gS21-2a8oS24-1e6bS01-1e6gS14-3e6bS30-2e8bC01-3c8oS16-1e9oC06-3c8oC07-3c6oC03-3c6oC05-3c8o

212186_at220668_s_at202532_s_at

218115_at203228_at

206074_s_at204826_at203967_at

211814_s_at212022_s_at

218308_at202240_at218755_at202954_at202338_at

202095_s_at203755_at

209644_x_at202735_at

209773_s_at210559_s_at

204825_at204092_s_at218883_s_at209172_s_at

207039_at217733_s_at

201890_at204170_s_at

218741_at218782_s_at204709_s_at205235_s_at

201202_at201088_at

211725_s_at208808_s_at

204146_at219493_at

217851_s_at218237_s_at

4F6-21

3-16 Genetic code

3 READING FRAMES

beta-globin(human)sequences

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 tRNA

6-8,9

4F6-65 3FtRNA

4F6-58

4F6-60

polyribosome

3F6-28,29

Central Dogma

Transcription

mRNA

Cells express different subset of the genesIn different tissues and under different conditions

Gene (DNA)

Translation

Protein