1. Ataxia- Telangiectasia and ATM
Kenji Leonard
3/5/2004
Cancer Biology

2. What is Ataxia-Telangiectasia
A-T is a progressive neurodegenerative genetic disease.
Cerebellar ataxia (In-coordination, lack of balance)
Ocular telangiectasia (Widening of small blood vessels in conjunctiva)
No cure and fatal by early 20s.

3. Cerebellar Ataxia

4. Ocular Telangiectasia
dec-99/99-dec-29.htm

5. What Causes A-T?
A mutated gene called ATM produces a mutated ATM protein (ataxia telangiectasia mutated)
Found by genetic linkage analysis
Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or LocusLink and/or Ensembl if different)                                                                  

7. Normal ATM protein Function
A Serine-Protein Kinase
Ex. p53, BRCA1
Senses Double Stranded Breaks in DNA
Activates cell cycle checkpoints

9. Abnormal ATM protein
70% of all mutated ATM protein is found to be truncated
Missense mutations produce a dominant negative effect
If heterozygous for mutated ATM gene, the cancer risk is 4X that of the general population

10. Abnormal ATM protein Function

11. ATM and cancer

12. Main Points
ATM, a serine kinase, senses DNA damage and activates cell cycle checkpoints to either arrest cell cycle or cause apoptosis.
Mutant ATM causes A-T, a genomic instability syndrome, which is lethal by age 20.
Mutant ATM heterozygotes have increased cancer risks.