UmuC D Lesion Bypass DNA Polymerase V

DNA is continuously damaged, which can eventually lead to mutations and cell death. This damage is bypassed by Y family DNA polymerases which are conserved throughout evolution and have the specialized ability to copy damaged DNA. Escherichia coli DNA polymerase V (pol V) is a Y family polymerase composed of UmuC, which is the polymerase subunit, and the UmuD′2 accessory subunit. UmuD′2C is known to bypass thymine–thymine dimers caused by UV radiation, as well as abasic sites that arise via multiple mechanisms. UmuD′2C is regulated as part of the SOS response and performs potentially mutagenic translesion synthesis (TLS) to replicate damaged DNA. Pol V of E. coli is a member of the error-prone Y family of DNA polymerases, which have the specialized ability to copy damaged DNA in a process known as ‘translesion synthesis’ (TLS). Pol V consists of the 48-kDa UmuC subunit, which possesses the polymerase activity, and the homodimeric accessory subunit UmuD′2 (12 kDa each), and is written as UmuD′2C. UmuD′ results from the self-cleavage of the slightly larger protein UmuD (15 kDa). Environmental and chemical mutagens, for example, ultraviolet (UV) radiation and mitomycin C, respectively, can cause damage to DNA and stress to cells. When this occurs, the cell initiates a response known as the ‘SOS response’, causing a cascade of events. The expression of the umuDC genes, encoding pol V, is induced as part of this response. This specialized polymerase bypasses common lesions from UV radiation, such as thymine–thymine (T–T) cis–syn cyclobutane pyrimidine dimers (CPD) and T–T (6–4) photoproducts, as well as abasic sites. Pol V and other members of the Y family are characterized by low processivity, low fidelity when copying undamaged DNA, and a lack of proofreading. The cofactors RecA, SSB, β processivity clamp, and γ clamp loader all facilitate TLS.