Cellular Defenses Against Radiation-Induced Carcinogenesis:

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NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
NER PATHWAY GENES GENE ALIASES DESCRIPTION CCNH cyclin H CDK7 cyclin-dependent kinase 7 CETN2 CALT CEN2 caltractin isoform 1 (Centrin 2) CKN1 CSA Cockayne syndrome 1 (classical) DDB1 damage-specific DNA binding protein 1 DDB2 damage-specific DNA binding protein 2 ERCC1 UV20 excision repair cross-complementing group 1 ERCC2 XPD excision repair cross-complementing group 2 ERCC3 XPB BTF2 GTF2H RAD25 TFIIH excision repair cross-complementing group 3 ERCC4 XPF RAD1 excision repair cross-complementing group 4 ERCC5 XPG UVDR XPGC ERCM2 excision repair cross-complementing group 5 ERCC6 CSB CKN2 COFS RAD26 excision repair cross-complementing group 6 GTF2H1 general transcription factor IIH, polypeptide 1 GTF2H2 general transcription factor IIH, polypeptide 2 GTF2H3 general transcription factor IIH, polypeptide 3 GTF2H4 general transcription factor IIH, polypeptide 4 LIG1 ligase I, DNA, ATP-dependent MNAT1 menage a trois 1 (CAK assembly factor) RAD23A HHR23A RAD23 homolog A RAD23B HHR23B P58 HR23B RAD23 homolog B RPA1 replication protein A1 RPA2 replication protein A2 RPA3 replication protein A3 XAB2 HCNP HCNP protein; XPA-binding protein 2 XPA XP1 XPAC XP complementation group A NCI REB <strong>Radiation</strong> Epidemiology Course, May 14, 2007 TJJ
Page 1 and 2: Cellular Defenses Against Radiation
Page 3 and 4: GOALS: • Provide an overall descr
Page 5 and 6: NCI REB Radiation Epidemiology Cour
Page 9 and 10: Cancer cells “evolve” into a hi
Page 11 and 12: WHY CHECKPOINTS Fidelity of cell di
Page 17 and 18: Cyclin/CDK complexes seem to be reg
Page 19 and 20: • At least two checkpoints are re
Page 21 and 22: DO DEFECTIVE CHECKPOINTS CAUSE CANC
Page 23 and 24: Radiation-Induced G2 delay in lymph
Page 27 and 28: Rothkamm and Lobrick, PNAS, 2003 NC
Page 29 and 30: Somatic Mutation and Cancer Environ
Page 31 and 32: Major DNA repair pathways: • Non-
Page 37 and 38: “… the failure of DNA repair in
Page 39: T. Lindahl and R.D. Wood, Science 2
Page 43 and 44: Mismatch repair associated tumors i
Page 45 and 46: Non-Homologous End Joining (NHEJ) N
Page 47 and 48: Illegitimate Recombination NCI REB
Page 49 and 50: TARGET THEORY NCI REB Radiation Epi
Page 51 and 52: A-T CELL CANCER CELL DEATH NCI REB
Page 53 and 54: OTHER TARGET QUESTIONS: • If DNA
Page 55 and 56: Mutations in Chk2 produce the Li-Fr
Page 57 and 58: CASE STUDY: Finding Molecular Targe
Page 63 and 64: Environmental Causes of BCC • UV
Page 65 and 66: UV DAMAGE TO DNA NCI REB Radiation
Page 67 and 68: NER PATHWAY GENES GENE ALIASES DESC
Page 69 and 70: Skin cancers have unique p53 mutati
Page 71 and 72: For BCC, PTCH may be even a bigger
Page 73 and 74: Gorlin Syndrome • Nevoid basal ce
Page 75 and 76: Verónica Martín, Graciela Carrill
Page 77 and 78: Taipale J and Beachy PA Nature 411:
Page 79 and 80: PTCH may play a role in cell cycle
Page 83 and 84: Aszterbaum et al. Nature Med. 5:128
Page 85 and 86: Shh, PTCH, and SUFU mutations produ
Page 87 and 88: Thomas et al., J. Postgrad Med. 49:
Page 91 and 92:
Veratrum californicum (corn lily) N
Page 93 and 94:
Frank-Kamenetsky et al. J. Biol. 1:
Page 95 and 96:
CONFOUNDERS: AGE SKIN COLOR DOSE NC
Page 97 and 98:
• A disease of accelerated aging.
Page 99 and 100:
Age-Dependent Reactive Oxygen Speci
Page 101 and 102:
SKIN COLOR GENETICS NCI REB Radiati
Page 103 and 104:
Am J Epidemiol 155: 614, 2002 Melan
Page 105 and 106:
Melanocortin 1 Receptor gene (MC1R)
Page 107 and 108:
SKIN COLOR GEOGRAPHY Photograph by
Page 109 and 110:
DOSE NCI REB Radiation Epidemiology
Page 111 and 112:
National Geographic Magazine April
Page 113 and 114:
Aging genes (I.e. non-DNA repair) A
Page 115 and 116:
RR for XP patients by age 8000 8000
Page 117 and 118:
Radiation as a Model Carcinogen:
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Cellular Defenses Against Radiation-Induced Carcinogenesis:

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