thoughts on hd and pbt2, page-12

Hi Skint,

This is just FYI for any other readers following the chain.

• The DNA-damage response is crucial for cellular life and for avoiding neoplasia. It
occurs by rapidly transducing the damage signal to many cellular systems, such as the
DNA-repair machinery and the cell-cycle checkpoints.
• Double-strand breaks (DSBs) in the DNA — deadly DNA lesions — mobilize an
intricate signalling network by activating the ATM protein kinase, which, in turn,
orchestrates this network by phosphorylating one or more key proteins in each of its
branches.
• Other protein kinases related to ATM (Ataxia Telangiectasia Mutated) carry out similar functions in response to other
genotoxic stresses, and some of them collaborate with ATM in the DSB response.
• ATM deficiency leads to ataxia-telangiectasia (A-T), a genomic instability syndrome,
the hallmarks of which — neurodegeneration, immunodeficiency, radiation sensitivity
and cancer predisposition — show the intimate connection between maintenance of
genome stability, cellular and tissue functioning, and cancer prevention.
• Certain types of ATM mutations seem to increase cancer predisposition in heterozygous
carriers. This adds ATM to the list of genes that have sequence variations with important
implications for public health, especially with regards to cancer epidemiology.