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Tug-of-cell war

February 10, 2004

Researchers at the School of Life Sciences, University of Dundee have
made an exciting new discovery on how cells regulate themselves and
prevent cancer as reported in Nature tomorrow (Wednesday). Dr Tomo
Tanaka and his team members, Drs Hilary Dewar and Kozo Tanaka have
uncovered a tug of war that cells use to collect their full complement
of correct chromosomes. The absence of this tug of war leads to
irregular cells, tumours, cancer and congenital disorders such as Down
syndrome.

How all daughter cells get all their chromosomes has until now been a
mystery. But now that the team know how cells collect their vital
information, they can explore how cells prevent cancers and other
diseases by ensuring proper chromosome inheritance during cell
division.

All human cells (except eggs and sperms) contain 46 chromosomes, all of
which carry vital genetic information. Because genetic information is
crucial for the proper function of cells for the organs and tissues that
they organise, all chromosomes must be precisely copied and separated
into two daughter cells during each cell division.

Dr Tanaka says: "As a cowboy catches a wild horse by his lasso, each
daughter cell captures chromosomes by a rope-like apparatus and then
drags them to her side before she finally divides from her sister. Our
data suggest that cells are able to know if they have captured the right
chromosomes or not by playing a tug-of-war game for them. This game is
possible because duplicated chromosomes still attach to each other when
they are captured by ropes. If cells do not feel a tug, they realise
that they have grabbed the wrong chromosomes. In this case, daughter
cells have to throw another rope toward a chromosome and repeat this
process until they capture the right one."

The research team has also identified an enzyme called Aurora as a key
regulator whose activity allows daughter cells to have this second
trial. Research has shown that if Aurora activity goes wrong, cancers
could occur.

Dr Lesley Walker, Director of Cancer Information, Cancer Research UK
says: "This work sheds light on how dividing cells ensure that the
genetic material is shared evenly between their daughter cells. By
understanding how healthy cells work, we can gain considerable insight
into what goes wrong in cancer. Thus world-class research like this is
crucial for increasing our understanding of the biology of cancer, and
could ultimately pave the way for new approaches to prevent and treat
the disease."

Dr Tomo Tanaka is a Wellcome Trust Career Development Fellow and
Principal Investigator in the Division of Gene Regulation and Expression
based in the Wellcome Trust Biocentre at the University of Dundee.

The research is funded by The Wellcome Trust and Cancer Research UK.

The study, entitled "Tension between two kinetochores suffices for
their bi-orientation on the mitotic spindle" is published by Nature
(online) on 11 February.

University of Dundee