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,N 6 -  Ade

7. Holliday junction Displaced strand

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

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

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

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(NH 2 )COOH Tyr HO-CH 2 -CH(NH 2 )COOH Ser HO-CH(CH 3 )-CH(NH 2 )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. Loop 2 Loop 4 Active form of Ras, bound to GTP analogue Inactive form of Ras, bound to GDP -CH 2 - replaces –O- in triphosphate

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

25. Ras structure and major features

26. Gly12Val mutant Ras WT Ras

27. Ras G12V Ras G12P Ras WT = Mg = H 2 O

28. Gln 61 WT Ras, with Gln 61 highlighted

29. Role of Gln 61 in GTPase activity of RAS

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

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 → TATSer → Tyr TCT → TTTSer → Phe

35. p34 = Cdc2

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

41. INK4 p16 INK4A p15 INK4B p18 INK4C p19 INK4D

42. Kip p21 Cip/WAF1 p27 Kip1 p57 Kip2

43. event pathwa y also p53