A protein that helps embryonic¹ stem cells (ESCs) retain their identity also promotes DNA² repair, according to a study in The Journal of Cell Biology. The findings raise the possibility that the protein, Sall4, performs a similar role in cancer cells, helping³ them fix DNA damage to survive chemotherapy. Fixing broken DNA is particularly important for ESCs because they will pass on any mutations to their differentiated⁴ descendants. Mouse ESCs are adept⁵ at making repairs -- they carry far fewer mutations than do differentiated cells -- but how they achieve this isn't clear. A team of researchers led by Yang Xu, from the University of California, San Diego, tested whether the protein Sall4, which suppresses differentiation⁶ of ESCs, has a role in DNA repair.

 

The researchers found that ESCs lacking Sall4 were poor at mending double-strand breaks, a hazardous⁷ form of DNA damage in which both strands⁸ of the double helix are severed⁹. They also observed that, after inducing DNA damage in mouse ESCs, Sall4 associated with proteins known to be involved in DNA repair. Overall, their findings support a model for how Sall4 is recruited to the sites of these breaks and activates¹⁰ ATM, a kinase that signals DNA damage and instigates¹¹ repair. Because tumor¹² cells often overexpress Sall4, the protein might similarly help them repair DNA damage. Sall4 could therefore be considered a target for drug development in cancer biology.

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