Structural insight into human Y-family polymerases and mechanistic basis of translesion synthesis of key DNA damages.

This review provides an accessible and mechanistically focused overview of the structural basis of human Y-family DNA polymerases and their roles in translesion synthesis (TLS) across diverse DNA lesions. The review highlights the unique structural features of these polymerases, including Polη, Polɩ, Polκ, and Rev1, and their specific mechanisms for navigating past DNA lesions including UV-induced CPDs, platinum drug-induced DNA damage, and alkylated DNA damage. Furthermore, structural insight are discussed to understand the structural mechanisms and fidelity differences among Y-family DNA polymerases during various lesion bypasses. Summarized findings on structural insight of bypass of various DNA lesions by Y-family polymerases represent TLS mediated mechanistic view of maintaining genomic stability and cancer cell survival, particularly under conditions of replication stress and DNA damage.