Annu. Rev. Genet. 2000. 34:479–97 Copyright c  2000 by Annual Reviews. All rights reserved THE SOS RESPONSE: Recent Insights into umuDC-Dependent Mutagenesis and DNA Damage Tolerance Mark D Sutton, Bradley T Smith, Veronica G Godoy, and Graham C Walker Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; e-mail: gwalker@MIT.EDU ■ Abstract Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B 1 . Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism’s genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur. Most bacteria, including Escherichia coli, have evolved a coordinated response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in (25) and also in (78,94)]. Re- cent advances have focused attention on the umuD + C + -dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis (70, 86). Here we discuss the SOS response of E. coli and concentrate in particular on the roles of the umuD + C + gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint. CONTENTS THE SOS RESPONSE ............................................. 480 The SOS Regulon ............................................... 480 Translesion DNA Synthesis and SOS Mutagenesis ....................... 482 DNA POLYMERASE ACTIVITY OF MEMBERS OF THE UmuC/DinB SUPERFAMILY ................................................ 482 The UmuC/DinB Superfamily ...................................... 482 UmuD + C + -Encoded DNA Polymerase Activity Is Necessary for DNA Synthesis in Vitro .............................................. 483 A Role for the umuDC Gene Products in Chromosomal Untargeted Mutagenesis .. 485 0066-4197/00/1215-0479$14.00 479 Annu. Rev. Genet. 2000.34:479-497. Downloaded from arjournals.annualreviews.org by NORTHEASTERN UNIVERSITY on 11/06/09. For personal use only.