Cancer cells activate damage-tolerant and error-prone DNA synthesis

Abstract

Trans-lesion synthesis (TLS) is a DNA damage-tolerant and error-prone mode of DNA replication. Recent work shows that many cancer cells coopt an aberrantly expressed germ cell protein, melanoma antigen-A4 (MAGE-A4), to activate TLS. MAGE-A4–induced “pathological TLS” provides a potential mechanism through which neoplastic cells can tolerate intrinsic and therapeutic genotoxicity while acquiring mutability.