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How antibody maturation evades DNA repair

In order to generate antigen-specific antibodies, the genes encoding immunoglobulins undergo processes that introduce mutations. These mutations result from deamination of dC to dU. However, it has not been clear how the DNA repair pathway that can reverse dU to dC does not function in this context. Two groups, led by Alberto Martin and Bernardo Reina-San-Martin, describe the isolation of an orphan protein, FAM72A, that is responsible for inhibiting the protein levels and activity of UNG2, a DNA glycosylase that removes uracil from DNA. This finding has broader implications as well, given that many cancers overexpress FAM72A, which would potentially increase the mutation load.

Nature Volume 600 Issue 7888

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