Guarding against collateral damage during chromatin transactions

Matthias Altmeyer and Jiri Lukas from Novo Nordisk Foundation Center for Protein Research are featured in the latest edition of Cell with a ‘Leading Edge minireview’ on molecular guardians that limit chromatin transactions.

Chromatin transactions confront cells with an exquisite challenge: cells need to elicit fast and strong responses to overcome physiological barriers and quickly adapt to changing conditions, yet they must keep these reactions in check to avoid excessive chromatin modification and signaling. Tipping the balance to either insufficient or to unrestrained reactions can have pathological consequences and cells have evolved to precisely balance benefits and risks.

This minireview highlights the emerging notion, that, in order to spatially and temporally confine DNA and chromatin transactions, which typically involve post-translational modification of key enzymatic components, cells cannot purely rely on reversion by counteracting enzymes. Instead, additional layers of control have evolved to limit chromatin transactions, at the cost of their immediate efficiency but with the long-term benefit of minimizing collateral damage in the form of unwanted alterations of the (epi)genetic code.

Here, the authors review recent research advances in the field and identify conceptual similarities of the molecular mechanisms that ensure the restriction of excessive chromatin responses involved in various types of chromatin transactions, including the DNA damage response, transcription, transposable elements, and chromosome end resection.

Finally, the authors outline the key future directions that they find would promote the generation of a holistic picture of the mechanisms that guard our genome from collateral damage and hence potential disease.

Title: Guarding against collateral damage during chromatin transactions

Authors: Matthias Altmeyer and Jiri Lukas

http://www.cell.com/fulltext Cell, Volume 153, Issue 7, 1431-1434, 20 June 2013