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Diseases

Molecular Genetics - Repairing the damage

There’s a whiteboard behind the desk of Jörg Heierhorst, head of SVI’s Molecular Genetics Unit. It’s covered in layers of swirling scribbles, numbers and formulae and words by the dozen, urgently expressed in green, blue, red and black marker.

Then, with an array of circles, curly brackets and arrows that sweep from one side of the board to the other, each of these ideas is connected to the others.

In Jörg’s world of molecular genetics, everything is connected to everything else. He and his group attempt daily to unravel the secrets locked inside our DNA at the most elemental level.

In conversation, with a soft Hamburg accent, Jörg explains how the DNA damage that underlies most cancers develops.

“Just as you would call an electrician if you have a problem with the wiring in your house, cells send an emergency call for specific types of proteins to repair specific types of DNA damage. It’s when these calls go unanswered that cancer develops.”

By studying these DNA repair mechanisms, Jörg’s team hope to uncover the underlying causes of cancer and to provide new approaches to recovery therapy.

They’ve already identified a new human DNA repair protein, called ASCIZ. It’s normally distributed diffusely throughout the nucleus, but when a cell is exposed to DNA-damaging agent, such as those found in some chemotherapeutic drugs, ASCIZ distributes itself to specific sites. ASCIZ then assembles DNA-damaging response machinery at these sites, making it an indispensable part of the repair process.

ASCIZ has also been implicated in repairing the damage caused by some chemotherapeutic drugs so it might also be a way of rendering chemotherapy more effective. In addition to these studies, SVI’s researchers are continuing their important work with DNA repair mechanisms in yeast, looking at:

  • How known DNA repair mechanisms work;
  • How cells stop other functions in order to repair damage;
  • How the yeast counterpart of ASCIZ, Mdt1, regulated the function of other proteins.

By identifying important new DNA repair response mechanisms, the work of SVI’s Molecular Genetics Unit may have wide ranging implications for our understanding of the onset and progression of cancer, and provide us with new options for more effective cancer treatments.