Answering the Call: Coping with DNA Damage at the Most Inopportune Time

Abstract

DNA damage incurred during the process of chromosomal replication has a particularly high possibility of resulting in mutagenesis or lethality for the cell. The SOS response of Escherichia coli appears to be well adapted for this particular situation and involves the coordinated up-regulation of genes whose products center upon the tasks of maintaining the integrity of the replication fork when it encounters DNA damage, delaying the replication process (a DNA damage checkpoint), repairing the DNA lesions or allowing replication to occur over these DNA lesions, and then restoring processive replication before the SOS response itself is turned off. Recent advances in the fields of genomics and biochemistry has given a much more comprehensive picture of the timing and coordination of events which allow cells to deal with potentially lethal or mutagenic DNA lesions at the time of chromosomal replication.

Figure 1

Clustered display of gene expression profiles following UV exposure in wild-type and lexA1 (SOS deficient) Escherichia coli [21]. Increased transcript levels are shown in red, decreased transcript levels are shown in green. The timepoints for irradiated samples (left to right) were 5, 10, 20, 40, and 60 minutes following UV irradiation. The timepoints for unirradiated samples (left to right) were 20 and 60 minutes following UV irradiation. All measurements are relative to time 0. Genes were selected for this analysis if their expression level deviated from time 0 by at least a factor of 2 in at least 3 time points. The colored image was produced using cluster analysis and is publicly available with this data at . The color scale ranges from saturated green for log ratios 2.0 and below to saturated red for log ratios 2.0 and above.