B cells pay a price

Mutation frequencies and AID activation state in B-cell lymphomas from Ung-deficient mice

“…Recently, inherited mutations in mouse or man in single or multiple genes encoding MYH and other DNA glycosylases, different from Ung, have been found to be associated with increased tumor frequencies in tissues such as colon, ovary and lung (for a review, see Barnes and Lindahl, 2004). As noted previously by Gearhart (2003), the association of an Ung deficiency in mice with B-cell lymphomas, but not other tumors, suggests that stochastic events associated with the unique molecular processing of antibody genes accounts for the appearance of malignant B-cell transformation in Ung-deficient mice. In Ung-negative cells, dU Á dG base pairs generated in antibody V genes by the Aid deaminase require the Msh2-dependent mismatch repair system for further processing (Rada et al, 2004); the apparently lower efficiency and longer repair patches of this back-up system by comparison with Ung-dependent base excision repair might be associated with an increased risk of error-prone alterations.…”