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| Reports on Overseas' Conferences and
Meetings |
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| Report on Ataxia
Telangiectasia Workshop 2008 |
| Motohiro Yamauchi, Department
of Molecular Medicine |
I participated in the Ataxia
Telangiectasia Workshop (ATW) at Lake Biwa,
22-26, April. The ATW is not a simple workshop
of “ATM protein”, but for the
purpose of the conquest of Ataxia Telangiectasia,
because the participants are not only basic
scientists, but also clinical doctors, a
representative of A-T Children’s Project,
and more, mothers of A-T affected children.
Sessions began from 8:00 AM, and finished
10:00 PM almost everyday, full of interesting
talks. Some of the presented data were unpublished,
and I obtained a lot of information in detail
concerning DNA damage response. Below, I
would like to introduce the talk of Dr. Penelope
Jeggo, which impressed me the most.
It has been well-known that more DNA double-strand
breaks (DSBs) remain in A-T cells than in
normal human cells. Previously, Dr. Jeggo’s
group reported that ATM is involved in 10-15%
of total DSB repair. From her data, she hypothesized
that ATM is involved in repair of DSBs in
heterochromatin, and tested the hypothesis.
First, she analyzed foci number of phosphorylated
histone H2AX in euchromatin and heterochromatin
in irradiated NIH3T3 cells, which exhibit
distinct heterochromatin region represented
by concentrated DAPI staining. And she found
that the decrease in foci number is slower
in heterochromatin than in euchromatin. Treatment
of ATM specific inhibitor (KU55933) made foci
decrease in heterochromatin slower, but it
did not change foci number kinetics in euchromatin.
Previously, Dr. Yosef Shiloh’s group
reported that in response to DSBs, chromatin
throughout the nucleus undergo relaxation
by dissociation of KAP1 from chromatin of
which process depends on phosphorylation by
ATM. Dr. Jeggo found that ectopical expression
of alanine-mutant KAP1 at ATM-dependent phosphorylation
site slows down foci decrease similarly to
the treatment of ATM inhibitor. Moreover,
ATM inhibitor did not change foci decrease
in Suv39H1/2(-/-) MEFs and ICF syndrome cells,
which have very few heterochromatin regions.
From these data, she concluded that ATM is
involved in repair of DSBs in heterochromatin.
What’s new of her study is the demonstration
of the ATM involvement in DSBs repair in heterochromatin.
It has already been clear that ATM contributes
to a fraction of DSB repair, but it was unknown
what kind of DSB requires ATM to be repaired.
From ATW, I realized it is not interesting
to follow the ATM authorities, and demonstration
of a hypothesis drawn by deep insight and
unique ideas makes research more thrilling.
Last but not least, I would like to express
my sincere appreciation for the financial
support of Global COE program and Dr. Shuninchi
Yamashita. |
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