Download Ataxia- Telangiectasia and ATM

Ataxia- Telangiectasia
and ATM
Kenji Leonard
3/5/2004
Cancer Biology
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.
Cerebellar Ataxia
Ocular Telangiectasia
www.indianpediatrics.net/ dec-99/99-dec-29.htm
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)
Normal ATM protein Function
A Serine-Protein Kinase
Ex. p53, BRCA1
Senses Double Stranded Breaks in DNA
Activates cell cycle checkpoints
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
Abnormal ATM protein Function
ATM and cancer
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.