Fanconi Anemia: Diagnosis and Treatment

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FANCD2 Monoubiquitination is a CriticalEvent in the FA pathwayBlot- anti-FANCD2(monoubiquitinated)FANCD2-LFANCD2-SwtFA-AFA-A+ +FANCAFA-CFA-C+F FANCCFA-GFA-G+F FANCGFA-F1 2 3 4 5 6 7 8 9FA-F+ +FANCFIF-anti-FANCD2(mutant)(corrected)
The Fifteen FA proteins regulate DNA crosslink repairduring S phaseE3 LigaseDNA Damagewith crosslinkin S phasePPID2I/D2 DissociatesFrom chromatinUbDNA RepairUbD2IUbI/D2 Associateswith chromatinMoldovan and D’Andrea,Ann Rev Genetics, 2009BRCA2NOJUbD2Ub I?USP1UAF1USP1/UAF1 activity isrequired for FanconiAnemia pathway
Page 3: Fanconi anemia history• Named aft
Page 6 and 7: Image courtesyDr Blanche Alter
Page 9 and 10: Image courtesyDr Blanche Alter
Page 12 and 13: Fanconi Anemia: Cellular phenotype
Page 14 and 15: Chromosome breakage read-outML# Ref
Page 16: The Fifteen Fanconi Anemia GenesGen
Page 24 and 25: BRCA2 is a Fanconi Anemia Gene (D1)
Page 26 and 27: In BRCA2 kindreds:dParadoxBRCA2 (+/
Page 28 and 29: Natural history of FA• Birth defe
Page 32 and 33: Pathophysiology• DNA repair Bone
Page 34 and 35: Treatment of Fanconi AnemiaAndrogen
Page 36 and 37: 100%90%Unrelated Donor BMT for FASu
Page 38 and 39: New treatments are badly needed•
Page 40 and 41: Alan D’AndreaJohn PostlethwaitMar
Page 42: mammary AC10 moovarian AC13 momamma
Page 45: Properties of tempol• Superoxide
Page 49 and 50: Conclusions• The SOD mimetic temp
Page 51 and 52: From:Maclean KH, Dorsey FC, Clevela
Page 53 and 54: Mean tumor-free survival:Placebo: 1
Page 57: Reduced numbers of stem cells
Page 60: Changes in cell cycle status of ste
Page 70 and 71:
SRT3025 (“SirT Diet”) treatment
Page 72 and 73:
Cancer Cells are often defective in
Page 74 and 75:
Cancer Cells are often defective in
Page 76 and 77:
Since 5-20 % of solid tumors in the
Page 78 and 79:
siRNA Targets Specifically Toxic to
Page 80 and 81:
FA Cell Lines Are Hypersensitive to
Page 82:
Conclusions:1) Conventional cancer
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Fanconi Anemia: Diagnosis and Treatment

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