Regulation of <i>Escherichia coli</i> SOS mutagenesis by dimeric intrinsically disordered <i>umuD</i> gene products

<jats:p> Products of the <jats:italic>umuD</jats:italic> gene in <jats:italic>Escherichia coli</jats:italic> play key roles in coordinating the switch from accurate DNA repair to mutagenic translesion DNA synthesis (TLS) during the SOS response to DNA damage. Homodimeric UmuD <jats:sub>2</jats:sub> is up-regulated 10-fold immediately after damage, after which slow autocleavage removes the N-terminal 24 amino acids of each UmuD. The remaining fragment, UmuD′ <jats:sub>2</jats:sub> , is required for mutagenic TLS. The small proteins UmuD <jats:sub>2</jats:sub> and UmuD′ <jats:sub>2</jats:sub> make a large number of specific protein–protein contacts, including three of the five known <jats:italic>E. coli</jats:italic> DNA polymerases, parts of the replication machinery, and RecA recombinase. We show that, despite forming stable homodimers, UmuD <jats:sub>2</jats:sub> and UmuD′ <jats:sub>2</jats:sub> have circular dichroism (CD) spectra with almost no α-helix or β-sheet signal at physiological concentrations <jats:italic>in vitro</jats:italic> . High protein concentrations, osmolytic crowding agents, and specific interactions with a partner protein can produce CD spectra that resemble the expected β-sheet signature. A lack of secondary structure <jats:italic>in vitro</jats:italic> is characteristic of intrinsically disordered proteins (IDPs), many of which act as regulators. A stable homodimer that lacks significant secondary structure is unusual but not unprecedented. Furthermore, previous single-cysteine cross-linking studies of UmuD <jats:sub>2</jats:sub> and UmuD′ <jats:sub>2</jats:sub> show that they have a nonrandom structure at physiologically relevant concentrations <jats:italic>in vitro</jats:italic> . Our results offer insights into structural characteristics of relatively poorly understood IDPs and provide a model for how the <jats:italic>umuD</jats:italic> gene products can regulate diverse aspects of the bacterial SOS response. </jats:p>