Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA.
Nucleic Acids Res. 2012 Jul;40(12):5511-22. doi: 10.1093/nar/gks229. Epub 2012 Mar 9.
DNA polymerase III (DNA pol III) efficiently replicates the Escherichia coli genome, but it cannot bypass DNA damage. Instead, translesion synthesis (TLS) DNA polymerases are employed to replicate past damaged DNA; however, the exchange of replicative for TLS polymerases is not understood. The umuD gene products, which are up-regulated during the SOS response, were previously shown to bind to the α, β and ε subunits of DNA pol III. Full-length UmuD inhibits DNA replication and prevents mutagenic TLS, while the cleaved form UmuD' facilitates mutagenesis. We show that α possesses two UmuD binding sites: at the N-terminus (residues 1-280) and the C-terminus (residues 956-975). The C-terminal site favors UmuD over UmuD'. We also find that UmuD, but not UmuD', disrupts the α-β complex. We propose that the interaction between α and UmuD contributes to the transition between replicative and TLS polymerases by removing α from the β clamp.
DNA 聚合酶 III（DNA pol III）能够有效地复制大肠杆菌基因组，但它不能绕过 DNA 损伤。相反，需要使用跨损伤合成（TLS）DNA 聚合酶来复制过去受损的 DNA；然而，复制酶向 TLS 聚合酶的转换尚不清楚。umuD 基因产物在 SOS 反应期间上调，先前已显示与 DNA pol III 的α、β和ε亚基结合。全长 UmuD 抑制 DNA 复制并防止诱变 TLS，而切割形式的 UmuD'促进诱变。我们表明，α 具有两个 UmuD 结合位点：在 N 端（残基 1-280）和 C 端（残基 956-975）。C 端位点偏爱 UmuD 而不是 UmuD'。我们还发现 UmuD 而不是 UmuD'破坏了α-β 复合物。我们提出，α 与 UmuD 之间的相互作用通过从β夹上除去α来促进复制酶和 TLS 聚合酶之间的转换。
