Body clock proteins may be cancer drug targets say researchers

The two proteins​ – Cry1 and Cry2 –are important for setting our circadian clocks; their expression is very high in the afternoon but very low when we sleep.

They also “play an important role in the response to DNA damage​” according to Katja Lamia​, author of new reseach who set out to investigate "whether they might regulate the expression of other genes known to be important in repairing DNA or responding to DNA damage, and we found this seems to be true. ​

The researchers began by going on a trawl using mass spectrometry to see which proteins bind strongly to these two clock proteins. 

They discovered one protein in particular – Hausp – that bound strongly to Cry1. This raised a red flag, as Hausp is known to be part of cells’ DNA repair responses.  It is known to remove a tag that marks proteins for destruction, and so can boost quantities of specific proteins by erasing such tags.

“We found the interaction between Hausp and Cry1 was increased after cells were exposed to different things that might cause mutations in DNA. By increasing this interaction, Cry1 stability increases and there is more around when DNA damage is occurring.  This suggests it may play a role in responding to damage​,” said Lamia.

Druggable​

A future therapeutic approach could look to increase levels Cry1 when needed, though a deeper understanding would be needed so as not to disrupt our biological clock. Cry1 is also known to be involved in regulating blood glucose. 

“You might be able to generate molecules that specifically target the role of these proteins, to basically enhance their ability to protect the genome from mutation.  You might want more Cry1 or Cry2 to hang around, or you might have something more specific like a small molecule to increase their interaction with a particular partner​,” Lamia said.

“Something that would help to avoid circadian disruptions is to use small molecules that could not cross the blood brain barrier.  That way you could have molecules that simply could not get into the brain and so shouldn't affect sleep brain cycles​.”