Transcript Document 271476

Brianna Eskola
Fanconi’s Anemia
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Autosomal recessive
Affects 1/100,000
Bone marrow disease
Loss of blood cells
Seen before age 12
Symptoms
 Abnormal heart, lungs, and
kidneys
 Bone problems
 Abnormal hands
 Pigment changes in skin
 Can lead to AML
 Squamous cell carcinomas
http://www.radswiki.net
Fanconi's Anemia Cells
 Elevated apoptosis
 Prolonged G2 phase
 Chromosome instability with telomere shortening
 Sensitivity to DNA interstrand crosslinks
bp1.blogger.com/.../s320/BreaksFanconi.gif
FANCD2 and the
FA
NCC
 Tumor Suppressor
 Highly conserved
 Primary role: recruit
FANCD1/BRCA2
 FA proteins;
FANCA/B/C/E/F/G/L =
nuclear core complex,
NCCFA
 The NCCFA complex
stabilizes replication forks
theyorf.com/fanconi-anemia
DNA crosslink
www.bioscience.org/2004/v9/af/1246/fig1.jpg
FANCD2 and FA protein pathway
theyorf.com/fanconi-anemia
DNA repair
FANCD2 Pathways
www.nature.com
Knockout Mice
 Fancd2 -/ Viable
 Sensitive to Mytomycin C
 Developmental delay
 More severe phenotype
than other FA mutants
 High incidence of tumor
development
 Do not develop Anemia
 Not due to ATM-dependent
S-phase checkpoint
Rad51 and Brca2 normal in FANCD2 Mutants
The Big Picture
Testing
Treatment
 Chromosome breakage test
 Regular blood count checks
 Complete blood count test
 Growth factors
 Bone marrow biopsy
 Bone marrow transplant
 Anti-biotics
 Blood transfusions
medical-genetics.net/Laboratory/Breakage.htm
https://www.blueshieldca.com
Review
 FANCD2 serves two purposes:
 Stalls the replication fork to recruit BRCA1 to repair
interstrand crosslinks in DNA
 To arrest cell in S-phase
 If FANCD2 mutated:
 Hypersensitive to DNA crosslinks with high rate of apoptosis
– anemia
 Avoid apoptosis creates clones with cytogenic defects–
cancer especially AML
References
 http://www.nlm.nih.gov/medlineplus/ency/article/000334.ht
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m - medicine plus
http://www.fanconi.org/aboutfa/FA.htm - Fanconi Research
Fund
theyorf.blogspot.com/2007/10/fanconi-anaemia-...
http://www.nature.com/nm/journal/v8/n6/full/nm0602555.html - nature medicine
Thompson, Larry H. et al. How Fanconi Anemia Proteins
Promote the Four Rs: Replication, Recombination, Repair, and
Recovery. 2005
Houghtaling, Scott. et al. Epithelial Cancer in Fanconi Anemia
Complementation Group D2 Knockout Mice. 2003