Caffeine and Apoptosis - Caffeine: Chemistry, Analysis, Function and Effects - page 390

Key Facts of ATM

N Ataxia telangiectasia is caused by mutations in the ATM gene located on
chromosome 11q22.23 in 1988 and it positional cloning by Savitsky et al in
1995.
N Ataxia telangiectasia usually runs in families. The mode of inheritance is
autosomal recessive, so in a family with two parents who are carriers of the
A-T allele, there is 1 chance in 4 for each child born to the parents to have
the disorder. Prenatal diagnosis can be carried out in most families, but this
is complex and must be arranged before conception.

d n 0 t 2 n g | 2

N

Cloning of full-length ATM cDNA was first accomplished in 1997.

N

c-Abl was identified as the ATM interacting protein in 1997.

N

p53 was identified as a substrate for ATM in radiation signal transduction
by different investigators.

N

The ATM gene encodes a 13kb mature transcript with an open reading
frame of 9168 nucleotides.

N

The ATM protein is about 370kDa, is ubiquitously expressed, and is
localized to the cell nucleus.

N

The ATM protein is a large serine-threonine kinase thought to play a role in
regulating cell cycle checkpoints, repair of double stranded DNA and
meiosis.

N

ATM is also known to play a role in regulating p53, BRCA1 and Chk2.
Part of ATM's role in DNA repair is known to be that of telomere repair
as telomeres degrade more rapidly in people affected with Ataxia

telangiectasia.

N

Atm-deficient mice exhibit growth retardation.

N

Both male and female Atm-deficient mice are infertile.

N

Atm -/- mice develop aggressive malignant thymic lymphomas and usually
succumb to the disease by 4 months of age.

N

Mice homozygous for Atm disruption display acute radiation sensitivity,
which is manifested selectively in certain tissues, including the gastro-
intestinal tract, salivary glands and skin.

Key Facts of Apoptosis

N In addition to cell-cycle arrest and repair machinery, the damaged cells,
where damage is beyond repair, may induce an apoptotic (programmed cell
death; PCD) response that is highly cell-specific and is the most common
form of physiologic cell death in multicellular forms.
N Apoptosis is described by its morphological characteristics, including cell
shrinkage, membrane blebbing, chromatin condensation and nuclear

fragmentation.

N

The concept of PCD was first developed by plant biologists in 1920s.