UmuD’2  -  UmuD’2

Biological function
The bacterial SOS response is a tightly regulated reaction to stress-induced DNA damage. It is temporally divided into an early, relatively accurate DNA repair phase and a later, more mutagenic damage-tolerance phase. This timing is regulated in part by products of the umuD gene. The initial product, UmuD2, is a homodimer composed of 139 amino acid subunits that appears early after SOS induction. Damage-induced RecA:ssDNA nucleoprotein filaments mediate a slow autocleavage of UmuD2 that is mechanistically similar to the inactivation of the LexA repressor. The N-terminal 24 amino acids of each subunit of UmuD2 are removed, leaving a homodimer of the C-terminal 115 amino acid subunits, UmuD’2. UmuD’2 activates UmuC, the catalytic subunit of the Y family DNA polymearse (Pol) V, for mutagenic translesion DNA synthesis (TLS). UmuD2 participates in a DNA damage checkpoint while the closely related UmuD’2 acts in translesion synthesis and inhibition of homologous recombination.

Structural evidence
Despite forming stable homodimers at a wide range of physiologically relevant concentrations, UmuD2 and UmuD’2 have circular dichroism (CD) spectra with almost no α-helix or β-sheet signal at physiological concentrations in vitro resembling that of a random coil. High protein concentrations, osmolytic crowding agents, and specific interactions with a partner protein can produce CD spectra that resemble the expected β -sheet signature.

Biochemical evidence
Some positions that are predicted to be far away from the dimer interface also cross-link. However, these residues can come together if the N-terminal arms are in an intermediate conformation. These results suggest that UmuD2 may interchange among multiple conformations in solution. Since the conformation of the N-termini is the major difference between UmuD2 and UmuD’2, contacts involving the N- terminal arms or the region of the core buried by the UmuD arm are expected to contribute to the distinctive interactions of UmuD’2. Indeed, most of the mutations that enhance UmuD’2C-dependent inhibition of homologous recombination lie within the N-terminal arms of UmuD’2, with E35K having the greatest effect on binding. Different contacts with DNA pol III enable UmuD’2 to promote translesion synthesis and UmuD2 to effect a DNA damage checkpoint.

Mechanism category
flexibility modulation/competitive binding

Fuzziness enables to adapt to multiple distinct protein–protein interactions of these gene products despite of the small size and posttranslational modifications further differentiate these interactions. UmuD2 and UmuD’2 may act as interchangeable interaction domains for the two Y family DNA polymerases in Escherichia coli, thus allowing for a streamlined genome while maintaining the regulatory sensitivity of the interaction module.