Is Ataxia Telangiectasia a Result of Impaired Coordination Between DNA Repair and Cell Cycle Checkpoint Regulators?
Adayabalam S. Balajee and Charles R. Geard
Ataxia telangiectasia (AT) is an autosomal recessive multisystem human disorder and
patients are characterized by cerebellar ataxia, oculocutaneous telangiectasia, immuno
deficiency, chromosomal instability and radio sensitivity with an increased predisposition
to lymphoid cancer in childhood. The gene responsible for AT, ataxia telangiectasia mutated
(ATM), has been cloned and its protein product has been biochemically characterized as
a serine/threonine kinase belonging to the family of phosphatidylinositol (PI-3) like kinases.
Subsequent biochemical studies by several laboratories have identified a number of DNA repair
and cell cycle proteins that are phosphorylated by ATM kinase in response to different
DNA damaging agents. One intriguing question that comes to mind is whether the phenotypic
features of AT stem from a DNA repair defect or a cell cycle defect or both. The scope of
this review is focused on the potential functions of ATM in both DNA repair and cell cycle
checkpoint regulation and how deficiencies in these overlapping functions can lead to some of
the phenotypic features of AT patients.