Transcription-Coupled DNA Repair in Prokaryotes - Progress in Molecular Biology - page 25

Transcription-Coupled DNA
Repair in Prokaryotes

Ann Ganesan, Graciela Spivak,
and Philip C. Hanawalt
Department of Biology, Stanford University,
Stanford, California, USA

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

II. Background: Genomic Heterogeneity in NER and the Discovery of TCR . . . 26

III. The Role of RNA Polymerase in TCR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

IV. The Role of Mfd in TCR................................................................. 29

V. The Role of UvrA in TCR ............................................................... 32

VI. The Role of UvrB in TCR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

VII. Other Examples of Transcription-Related DNA Damage Processing in
Bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

A. NusA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

B. Base Excision Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

VIII. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Transcription-coupled repair (TCR) is a subpathway of nucleotide excision
repair (NER) that acts specifically on lesions in the transcribed strand of
expressed genes. First reported in mammalian cells, TCR was then documen-
ted in Escherichia coli . In this organism, an RNA polymerase arrested at a
lesion is displaced by the transcription repair coupling factor, Mfd . This protein
recruits the NER lesion-recognition factor UvrA , and then dissociates from the
DNA. UvrA binds UvrB, and the assembled UvrAB* complex initiates repair.
In mutants lacking active Mfd , TCR is absent. A gene transcribed by the
bacteriophage T7 RNA polymerase in E. coli also requires Mfd for TCR. The
CSB protein (missing or defective in cells of patients with Cockayne syndrome,
complementation group B) is essential for TCR in humans. CSB and its
homologs in higher eukaryotes are likely functional equivalents of Mfd .

I. Introduction

Nucleotide excision repair (NER), an intensively studied DNA repair
mechanism, was discovered in Escherichia coli and is now believed to occur
in essentially all living organisms. The major features of the genetic control of
NER and the biochemical pathways involved have been well documented;