Missing DNA 'mechanic' key driver in lymphomas

Cancer Research UK

CANCER RESEARCH UK scientists have discovered how a protein in immune cells plays an essential role in their development by repairing DNA damage - and if this protein is missing lymphomas can form.

The research, published online in Cancer Cell today1, showed that the protein, called ATMIN, acts as a cell’s ‘mechanic’ looking out for damage in DNA. When it spots damage, ATMIN prompts the cell to repair the DNA by recruiting another protein called ATM.

But without ATMIN, B cells2 do not recognise DNA damage and are unable to activate ATM to begin repairs. Instead the cell attempts to use different repair processes not designed to mend this damage.

This botched repair results in mistakes, causing parts of the DNA structure to be permanently damaged through deletions, gaps and breaks in the sequence. And as these cancer causing changes to the DNA structure accumulate, B cell lymphomas form.

Lead researcher, Dr Axel Behrens from Cancer Research UK’s London Research Institute, said: “Our findings reveal more about how this cellular ‘mechanic’ keeps DNA damage in check in the cell. ATM normally responds to changes in chromatin – the structure that packages the DNA into the cell – by repairing damage. Or if the damage can’t be repaired, ATM prevents the cell from replicating and ‘scraps’ the cell. But, critically ATM can only work if switched on by ATMIN.”

The researchers also found that ATMIN appears to play a role in human B cell acute lymphoblastic leukaemia (B-ALL). It is present only at very low levels in B-ALL cells compared to normal cells, suggesting that these findings could have a real impact on understanding the disease.

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “Revealing the inner workings of cells is essential to understanding how cancers develop. Understanding the role that ATMIN plays will be crucial in developing new and better treatments for lymphomas.”

ENDS

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References

1. Loizou et al,. ATMIN is required for maintenance of genomic stability and suppression of B Cell lymphoma, Cancer Cell (2011)

Notes to Editor

2. B cells are a type of lymphocyte, a key part of the immune system. Their role is to make antigens in response to pathogens that invade the body. It is errors in these cells that lead to lymphomas.