Regulation of E. coli SOS mutagenesis by dimeric intrinsically disordered umuD gene products

Products of the umuD gene in E. coli are involved in regulating the timing of error-free DNA repair processes and mutagenic translesion DNA synthesis (TLS) during the SOS response to DNA damage. Homodimeric UmuD2 is upregulated early during the SOS response, and a slow post-translational autocleavage process removes the N-terminal 24 amino acids of each UmuD monomer. The remaining C-terminal fragment, UmuD'2, activates the catalytic subunit of the Y family DNA polymerase V for mutagenic TLS. The small proteins UmuD2 and UmuD'2 make a large number of specific protein-protein contacts for their roles in regulation. This report chronicles experiments that indicate that umuD gene products share characteristics with intrinsically disordered proteins, which lack a defined secondary or tertiary structure when purified and many of which have important roles in regulation. Counterintuitively, UmuD2 and UmuD'2 form stable homodimers in vitro at concentrations where little or no a helix or 13 sheet is detectable. High protein concentrations and certain crowding agents can confer more typical secondary structure on UmuD2 and UmuD'2.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Simon, Sharotka M. (Sharotka Maria)

Advisor dc:contributor.advisor

• Graham C. Walker.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/38994

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/38994