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Abstract

The DNA double-strand break (DSB) is the most cytotoxic lesion and compromises genome stability. In an attempt to efficiently repair DSBs, cells activate ATM kinase, which orchestrates the DNA damage response (DDR) by activating cell cycle checkpoints and initiating DSB repair pathways. In physiological B cell development, however, programmed DSBs are generated as intermediates for effective immune responses and the maintenance of genomic integrity. Disturbances of these pathways are at the heart of B cell lymphomagenesis. Here, we review the role of DNA repair and cell cycle control on B cell development and lymphomagenesis. In addition, we highlight the intricate relationship between the DDR and the tumor microenvironment (TME). Lastly, we provide a clinical perspective by highlighting treatment possibilities of defective DDR signaling and the TME in mantle cell lymphoma, which serves as a blueprint for B cell lymphomas.