Researchers at the UW Medical School have found that mutations in a
gene they've been studying for several years can cause
ataxia-telangiectasia (A-T). The affected gene appears to play a
crucial role in controlling the way cells respond to DNA damage that
can lead to cancer.
The report, issued with Malcolm Taylor, a researcher from the United
Kingdom, appears in the Dec. 10 issue of Cell.
A-T is a genetic disorder that produces progressive nerve and muscle
loss. People with A-T are extremely susceptible to cancer. They can
become severely ill if they undergo radiation therapy and some may
even be harmed by exposure to low levels of radiation associated with
On the cellular level, genetic defects related to A-T produce DNA
instability and damage. DNA repair mechanisms in A-T patients don't
work properly, which can throw cells into serious disarray ending in
Scientists previously had identified mutations in a single gene, called
ATM, as the cause of A-T, but the UW team, led by associate professor
of genetics John Petrini, now reports that mutations in a closely
linked neighboring gene, called Mre11, can also independently produce
Petrini's team was the first to identify and describe the Mre11
complex, a protein cluster responsible for detecting DNA damage
within cells and thereby alerting them that damage is present.
"We can now definitively say that cooperation between Mre11 and ATM
comprises a critical component of the regulatory network that cells
activate in response to DNA damage," Petrini said. "Since mutations
in this complex affect normal development as well as the ability of
cells to respond to DNA damage, we infer that this network is also
important for normal growth control and cancer prevention."
The UW team reported last year that mutations in a different member of
the Mre11 complex, a gene called Nbs1, causes the genetic disease
Nijmegen Breakage Syndrome, which closely resembles A-T.