Regulating Insensitivity To DNA Damage

In most cells, DNA damage triggers 'sensors' to halt cellular activity until the DNA damage is repaired. Ari Melnick and colleagues find that the protein Bcl-6 prevents the production of the DNA damage sensor, called ATR, in a select group of B cells called germinal center (GC) cells, which produce antibodies. In this setting Bcl-6 is beneficial to B cells that encounter foreign antigen and then undergo highly focused DNA mutations in antibody-encoding genes, a process normally required to generate highly effective antibodies. However, such DNA mutations can also lead to GC B cell death, potentially reducing the production of useful antibodies.

Melnick's group shows that Bcl-6 can suppress activity of the ATR gene, which effectively 'turns off' the DNA damage sensor machinery and leaves the mutated GC B cells less prone to DNA damage-induced death. More generally, many B cell lymphomas display deregulated Bcl-6 expression and tolerate excessive DNA mutations, including those generated by radiation treatments. The new work suggests that manipulating Bcl-6 in lymphoma cells might render them more sensitive to irradiation.

Author contact:

Ari Melnick (Albert Einstein College of Medicine, Bronx, NY, USA)
Email: amelnick@aecom.yu.edu

Abstract available online.

(C) Nature Immunology press release.

Message posted by: Trevor M. D'Souza