1. 22% Pre-2001 (HGP) Cases of genetic pre-determinism are rare. Gene regulation allows for adaptation to environmental changes for an individual organism in the present. Mutations allow for adapatation to environmental changes for a species over generations Epigenetic changes allows for adaptation to current environmental changes for an individual organism to be passed on to its offspring.

2. Phage 15 coat proteins Infects E. coli 50,000 bp ds DNA

3. E Coli cell Phage binds to Cell membrane.......... and inserts dsDNA into cell In the lytic phase the cell replicates the phage DNA New phage particles are created …. Then the cell is lysed and the virus is released to the environment to seek new hosts.

4. Petri Dish with Nutrients With bacterial growth Add phage – plaque forms

5. E Coli cell Lysogenic Phase DNA inserted into bacterial chromosome Dormant phage’s DNA Copied with each bacterial cell division cycle.

6. Petri Dish plaques E. Coli cells (lysogenic) reclaim plaque areas, but give ‘turbid’ appearance. Lysogenic E Coli cells are immune to phage infection. DNA damage can be induced by UV light and causes switch from lysogenic to lytic phase.

7. yes Lytic Is host DNA Damaged? (UV) no Lysogenic Dormancy phage infects E coli Cell very early phase (N/cro) early phase (cII/cIII) Is host well fed?

8. |=12=10|=10=cIII=N=O L =cI=O R =cro=cII=2=Q=3=| att |=10=cIII=N=O L =cI=O R =cro=cII=2=Q=3=|=12=10| cos attahed to host chromosome in host unattached in virus particle

9. 2 = Replication genes 3 = Lysis genes 12 = Tail Protein genes 10 = Head Protein genes Lytic Phase 10: = 8 == Int == Xis == Lysogenic phase PIPI |=10=cIII=N= O L =cI=O R =cro=cII=2=Q=3=|=12=10| cos P RM P R P RE PIPI PLPL

10. REGULATORY GENES cI: ( Repressor) & Activator (favors lysogenic phase) cII: Activator (favors cI production over cro & Int) cro: activator & repressor (favors lytic phase) cIII: protects cII from proteases N & Q: antiterminators – bypass transcription stop signal |=10=cIII=N= O L =cI=O R =cro=cII=2=Q=3=|=12=10| cos P RM P R P RE PIPI PLPL

11. P I P L P RM P R P RE P R ’ LYS = cIII = N = O L = cI = O R = cro = cII = Q=Lyt cro +- cro - P I P L P RM P R P RE P R ’ LYS = cIII = N = O L = cI = O R = cro = cII = Q=Lyt cI - cI + - cII + lysogenic lytic

12. yes Lytic no Lysogenic Dormancy phage infects E coli Cell very early phase (N/cro) early phase (cII/cIII) Is host well fed? ↓[bacetrial protease] allows cIII time to protect cII. cI eventually dominates cro, and Int production. Int inserts phage DNA into host chromosome. ↑[bacetrial protease] destroys cII and cro dominance over cI is maintained.

13. P I P L P RM P R P RE P R ’ LYS = cIII = N = O L = cI = O R = cro = cII = Q=Lyt <<< P RM P R >>> OR1OR1 OR2OR2 OR3OR3

14. DNA double helix B Form major groove minor groove

15. N N N N N N N O O HCH 3 A T Major Groove Minor Groove H H

16. N N N N N N N O O HCH 3 T H H Gln CH 2 N H O=C CH 2

17. R R R Hydrophobic Contact H-bonds to Major Groove  -Turn HTH Motif

18. Zn H H C C Major Groove H-bonds Zinc Finger Motif

19. | | | | | L L L L L | | | | | L L L L L H-bonds to Major Grooves Leucine Zipper Motif

20. Lambda Phage Repressor Protein

21.  cro cro dimer cI dimer <<< P RM P R >>> OR1OR1 OR2OR2 OR3OR3 1st on 2nd on O R 1 1 1 O R 2 1 1 O R 3 10 (10) 1st on 2nd on O R 1 10 --- O R 2 1 5 O R 3 1 1

22. |=10=cIII=N=cI=O R =cro=cII=2=Q=3=|=12=10| cos <<< P RM P R >>> OR1OR1 OR2OR2 OR3OR3 cro 1st on 2nd on O R 1 1 1 O R 2 1 1 O R 3 10 (10) RNA Pol cro is expressed, cI is repressed.

23. |=10=cIII=N=cI=O R =cro=cII=2=Q=3=|=12=10| cos <<< P RM P R >>> OR1OR1 OR2OR2 OR3OR3 cro High [cro] represses both P RM & P R cro

24.  P RM PR PR  OR1OR1 OR2OR2 OR3OR3  -repressor binding blocks P R  1st on 2nd on O R 1 10 --- O R 2 1 5 O R 3 1 1 RNA Pol … and activates  P RM

25. |=10=cIII=N=cI=O R =cro=cII=2=Q=3=|=12=10| cos <<< P RM P R >>> OR1OR1 OR2OR2 OR3OR3  High [cI] represses P R & P RM 

26. Yes – SOS reponse genes activated Lytic Is host DNA Damaged? (UV) no Lysogenic Dormancy phage infects E coli Cell very early phase (N/cro) early phase (cII/cIII) [cI] remains high. Phage remains dormant. cI inhibits growth of any late-coming phage.

27. E coli SOS Response E coli contains 17 SOS genes — e.g. HSPs encode DNA repair/recombination genes — LexA & RecA LexA Repressor of SOS operon LexA contains HTH motif & similar AG sequence to cI HTHHTH

28. RecA Function Low [ ] under ‘normal’ circumstances binds to ssDNA: complex cleaves LexA at AG  [RecA] - ssDNA + ATP  dsDNA + ADP If  phage lysogen then RecA cleaves cI and induces lytic phase shift

29. yes Lytic Is host DNA Damaged? (UV) no Lysogenic Dormancy phage infects E coli Cell very early phase (N/cro) early phase (cII/cIII) ↑RecA-ssDNA destroys cI, and [cro] recovers dominance over cI. Xis expression removes phage DNA from host chromosome. Lytic phase commences. [cI] remains high. Phage remains dormant. cI inhibits growth of any late-coming phage.

30. Transformed Cell Characteristics 1. Telomere length maintained — (telomerase active) 2. Rapid cell growth/division 3. Apoptosis pathway disabled — ↓ p53/Rb (retinoblastoma protein) Artificial Cancer Cell — requires addition of 3 genes 1.sv40 virus T antigen blocks expression of tumor suppressor genes p53 & RbA (prevents apoptosis) 2. Ras oncogene – initiates unregulated cell growth 3. TERT – maintain telomere length 90% of all tumors express telomerase (ALT)

31. Cell Growth/Differentiation — Oncogenes 1. Growth Factor (sis) binds Receptor (erbB) - autophosphorylates Tyr residues 2. Phosphorylated receptor activates G-Protein (ras).... 3....activates Cytosolic Tyr Kinase (src) 4....  expression of transcriptional activators/repressors (myc) etc... Genes that can lead to cell transformation (cancer) when the gene product is underexpressed, overexpressed or mal-functioning (either overactive, underactive, or inactive).

32. Protooncogenes  Oncogenes 1. Altered function due to mutation 2. Altered expression - amount or timing e.g. mutation to activator/repressor protein 3. Altered expression due to transposition e.g. myc gene chrom 8  14 in Burkett’s Lymphoma.