“…Nevertheless, there is also a significant diversity in active site structures and detailed mechanisms of TLS polymerases, with different TLS enzymes specialized on a bypass of distinct types of DNA damage (cognate lesions). ,,− The prominent example is accurate and efficient bypass of the most common UV-induced DNA lesion, TT cyclobutane pyrimidine dimers (TT-CPDs), by polη. − TT-CPDs can also be copied over by other TLS enzymes in a less accurate, more mutagenic manner; , therefore, loss of polη activity in xeroderma pigmentosum variant (XPV) patients results in hypersensitivity to sunlight and predisposition to skin cancer. , Additionally, polη is proficient in nucleotide incorporation opposite intrastrand G–G cross-links caused by cisplatin (cisPt-GG), ,− and a number of other lesions . Another Y-family TLS polymerase, polκ, can also insert nucleotides opposite various lesions, as well as extend the aberrant DNA primer terminus; , most notably, it can efficiently and accurately bypass N 2 -dG adducts such as those formed by benzo[ a ]pyrene (BaP-G) present in tobacco smoke. − Polι is the least accurate TLS enzyme related to polη, ,, which uniquely utilizes Hoogsteen pairing of the incoming nucleotides with the template bases and often misincorporates dGMP opposite T bases. , Catalytic activity of Rev1 is limited to dCMP incorporation across G-templates and abasic sites, − while the B-family polymerase polζ primarily specializes in extension of the distorted primer-template following sites of DNA damage, − ,, but can also incorporate nucleotides across certain DNA lesions. − …”