A molecule originally implicated in DNA repair may also be a
crucial factor in preventing tumours such as medulloblastoma, a
type of childhood brain tumour, according to research from Cancer
Research UK's London Research Institute (now part of the
Francis Crick Institute).
The molecule, called RTEL1, is known to be responsible for
maintaining the ends of our chromosomes, the structures that
contain the genetic material DNA. Now scientists have discovered
that it also plays a critical role throughout the entire
genome.
Dr Simon Boulton and his team found that RTEL1 works together
with another molecule called PCNA. Like a hair tie, RTEL1 helps
PCNA as it forms a ring around the DNA allowing it to remove knots
and untangle DNA as it gets copied. This process is essential for
correctly copying DNA, so that cells can grow and divide without
making genetic mistakes.
When RTEL1 contains a fault preventing it from binding to PCNA,
DNA replication is disrupted and mistakes are made, which can lead
to cancer. When the researchers looked in mice whose RTEL1 gene was
flawed in this way, they found a substantial increase in the
incidence of several types of cancer, including lymphoma and
medulloblastoma, the most common type of childhood brain
cancer.
Previous studies had shown that there was a potential link
between RTEL1 and brain cancers, although it wasn't understood why.
This study confirms that RTEL1 is definitively involved in
preventing cancer by stopping mistakes from being made during DNA
replication, but more research is needed to understand why it
appears to be particularly associated with brain tumours.
Dr Boulton said: "This research exemplifies why it's so
important to study fundamental cellular processes in model systems.
With the aid of new technologies, we have uncovered an unexpected
role for the RTEL1 protein, and shown that this new role in
maintaining and replicating DNA may hold the key to some types of
cancer."
Dr Kat Arney, Cancer Research UK's senior science communications
manager, said: "Unravelling the inner workings of cancer cells is
essential if we are to truly make progress in beating cancer. This
is an important step forward in understanding the molecular
machinery that copies our DNA and what happens when it goes wrong.
And it could open the door to future approaches for prevention,
diagnosis or treatment."
The paper, RTEL1
Is a Replisome-Associated Helicase That Promotes Telomere and
Genome-Wide Replication, is published inScience.