TY - BOOK AU - Shachar,S. AU - Ziv,O. AU - Avkin,S. AU - Adar,S. AU - Wittschieben,J. AU - Reißner,T. AU - Chaney,S. AU - Chaney,S. AU - Wang,Z. AU - Carell,T. AU - Geacintov,N. AU - Livneh,Z. TI - Two-polymerase mechanisms dictate error-free and error-prone translesion DNA synthesis in mammals N2 - DNA replication across blocking lesions occurs by translesion DNA synthesis (TLS), involving a multitude of mutagenic DNA polymerases that operate to protect the mammalian genome. Using a quantitative TLS assay, we identified three main classes of TLS in human cells: two rapid and error-free, and the third slow and error-prone. A single gene, REV3L, encoding the catalytic subunit of DNA polymerase f (polf), was found to have a pivotal role in TLS, being involved in TLS across all lesions examined, except for a TT cyclobutane dimer. Genetic epistasis siRNA analysis indicated that discrete two-polymerase combinations with polf dictate error-prone or error-free TLS across the same lesion. These results highlight the central role of polf in both error-prone and error-free TLS in mammalian cells, and show that bypass of a single lesion may involve at least three different DNA polymerases, operating in different two-polymerase combinations UR - https://drive.google.com/file/d/1Wqf0FvzoMe0XzMNY2ptdW7qTgUVU-8A2/view?usp=drivesdk ER -