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radiation-induced DNA damage changes
during development. Models for the
interaction of the RAD54 protein and
DNA sparked much interest and debate,
proving there is still much for us to learn
and understand.
Award lectures
Throughout the two-day meeting, the
colloquium lectures were punctuated by
Biochemical Society award lectures.
Kiyoshi Nagai (Medical Research Council
Laboratory of Molecular Biology,
Cambridge, UK) presented a tour de force
describing his studies on the structure and
function of the pre-mRNA splicing
machinery. To obtain these 3D structures,
he described how several proteins had to be
expressed simultaneously for active
(correctly folded) assemblies to be formed.
The stunned audience clearly appreciated
the momentous task, which had not only
been attempted but had also been achieved.
Descriptions of the complexes of seven
proteins and two RNA fragments struck a
chord with many of those interested in DNA
repair because of the common knowledge
that these enzymes do not operate in
isolation. The inspirational qualities of
Nagai’s work will hopefully trigger similar
structural studies on DNA repair proteins.
The second of the award lectures was
given by John Sulston (Sanger Centre,
Cambridge, UK). The audience were fully
aware of Sulston’s reputation as his talk
was to be about the human genome
project. The draft sequence of the human
genome had been announced in June
2000, with much publicity and fanfare.
Although the sequence is still incomplete
and will be for some years, the vast
majority is now available. However, even
this partial achievement has created
overwhelming interest, probably because
the findings of this study have gross
implications on society today and in the
future. From a scientific standpoint, the
human genome project will aid our
understanding of, and our ability to cure,
genetic disorders, cancers and hereditary
diseases. From a political and social
standpoint, the project brings concerns
such as genetic cloning and even biological
warfare. However, fewer genes than were
expected have been found from the first
pass analysis, indicating that much more
DNA sequence needs to be analysed and
interpreted.
These and other talks left us with the
view that we have so much more to learn
about DNA repair. In addition, studies
such as those highlighted by the award
lectures can help us reach our goal and,
hopefully, improve our way of life.
Although numerous proteins are induced
in response to DNA damage, there are
probably several other proteins important
in genome maintenance and perpetuation
that have not yet been identified by
genetic or biochemical approaches. A
clearer vision of the way that DNA repair
proceeds will have a significant impact on
management of medical conditions.
References
1 Hanaoka, F. (2001) SOS polymerases. Nature
409, 33–34
2 McKenzie, G.J. et al. (2000) The SOS response
regulates adaptive mutation. Proc. Natl. Acad.
Sci. U. S. A. 97, 6646–6651
3 Napolitano, R. et al. (2000) All three
SOS-inducible DNA polymerase (Pol II, PolIV and
Pol V) are involved in induced mutagenesis.
EMBO J. 19, 6259–6265
4 McGlynn, P. et al. (2000) Characterisation of the
catalytically active form of RecG helicase. Nucl.
Acids Res. 28, 2324–2332
5 Venkitaraman, A.R. (2000) The breast cancer
susceptibility gene, BRCA2: at the crossroads
between DNA replication and recombination?
Phil. Trans. R. Soc. Lond. B. 355, 191–198
Jon R. Sayers* Dipak PatelDivision of Genomic Medicine, University ofSheffield, Royal Hallamshire Hospital,Sheffield, UK S10 2RX.
*e-mail: [email protected]
TRENDS in Biochemical Sciences Vol.26 No.3 March 2001
http://tibs.trends.com
150 Research Update
Axel Innis is a PhD student at the Dept of Biochemistry, University of Cambridge, UK.
What does the human genome sequence mean to you?
For a thorough and independent analysis of the meaning and importance of the February publications of thedraft human genome sequences, visit http://news.bmn.com/hmsbeagle/96/notes/feature3. To mark theimportance of the event, we are pre-publishing a number of Trends articles on these publications in our free,online magazine, HMS Beagle. You cannot afford to miss these up-to-the-minute commentaries, opinions andupdates, written by leading players from across the whole of biology. And they’re free!
