Lysine at 249 displaces 8-oxoGua from C1’ (arrow)

1. Lysine at 249 displaces 8-oxoGua from C1’ (arrow)

2. C1' HUMAN MITOCHONDRDIAL URACIL GLYCOSYLASE (UDG), WITH GLYCOSIDIC LINKAGE HYDROLYZED

3. human alkyladenine glycosylase (AAG) complex with DNA modified by tricyclic base 1,N6-Ade

7. Displaced strand Displaced strand Displaced strand Holliday junction

9. BACTERIAL REPAIR BY RECOMBINATION Eukaryotic homologues to RecA are characterized in yeast: DMC1 and RAD51

10. Repair of double-strand breaks Some Proteins Involved in Eukaryotic Repair General Strategy

13. E. coli UmuC/D (pol V) UmuC/D Error-prone extension of DNA from mispair opposite damage pol  pol-η Error-prone bypass of highly distorting or non-instructional lesions pol-

14. pol η complexed to cisplatin N7-cross linked GG: 3′ elongation step

15. pol η complexed to cisplatin N7-cross linked GG: 5′ elongation step

18. HO--CH(NH2)COOH Tyr HO-CH2-CH(NH2)COOH Ser HO-CH(CH3)-CH(NH2)COOH Thr

20. EGF = epidermal growth factor MEK = mitogen activated protein kinase/extracellular signal regulated kinase ERK = extracellular regulated kinase SOS also called GNRF (guanine nucleotide release factor

21. Raf, or effector activating Raf

23. Inactive form of Ras, bound to GDP Active form of Ras, bound to GTP analogue Loop 2 Loop 2 -CH2- replaces –O- in triphosphate Loop 4 Loop 4

24. Ras complexed to GTP analogue Ras complexed to GDP Loop 1 (P-loop) Loop 1 (P-loop) Loop 2 Switch I Loop 2 Switch I Loop 4 Switch II Loop 4 Switch II

25. Ras structure and major features

26. WT Ras Gly12Val mutant Ras

27. Ras WT Ras G12V = Mg = H2O Ras G12P

28. WT Ras, with Gln 61 highlighted Gln 61

29. Role of Gln 61 in GTPase activity of RAS

30. KINASE ACTIVITY OF V599E B-Raf BAY 43-9006 P-loop P-loop Phe467 Phe467 Glu599 Val599 Ser615 (kinase domain – green) WT B-Raf V599E B-Raf

31. Role of β-catenin protein in the Wnt signaling pathway In the absence of signal, action of the destruction complex (CKIα, GSK3β, APC, Axin) creates a hyperphosphorylated β-catenin, which is a target for ubiqitination and degradation by the proteosome. Binding of Wnt ligand to a Frizzled/LRP-5/6 receptor complex leads to stabilization of hypophosphorylated β-catenin, which interacts with TCF/LEF proteins in the nucleus to activate transcription.

32. Structure of residues 19 – 44 of β-Catenin phosphorylated on Ser 33 and 37 Oncogenic mutations in codon 33: TCT → TAT Ser → Tyr TCT → TTT Ser → Phe

35. p34 = Cdc2

38. Initial response of yeast to DNA damage in G1, S, G2 phases • homologues • yeast human • TEL1 ATM • MEC1 ATR • RAD53 Chk2

41. INK4 p16INK4A p15INK4B p18INK4C p19INK4D

42. Kip p21Cip/WAF1 p27Kip1 p57Kip2

43. event pathway also p53