Are there DNA damage checkpoints in E. coli?

Abstract

The concept of regulatory 'checkpoints' in the eukaryotic cycle has proved to be a fruitful one. Here, its applicability to the bacterial cell cycle is examined. A primitive DNA damage checkpoint operates in E. coli such that, after exposure to ultraviolet light, while excision repair occurs, chromosome replication continues very slowly with the production of discontinuous daughter strands. The slower the rate of excision of photoproducts, the greater the delay before the normal rate of DNA replication is restored, the additional time for repair ensuring that normal survival is maintained. A model is proposed in which replication rate is controlled by the ratio of RecA-coated to uncoated single stranded regions of DNA in the replication fork. There are also two cell division inhibitors SulA (= SfiA) and SfiC under the control of the SOS system and sensitive to DNA damage, but they are irrelevant to the survival of wild-type bacteria under normal conditions. In strains where SulA and SfiC do not operate, inhibition is not influenced by the rate of excision repair and so fails one of the criteria for a DNA damage checkpoint, namely the monitoring of the DNA for the level of residual damage.

A model for a umuDC -dependent prokaryotic DNA damage checkpoint

“…Bridges (50) has hypothesized that the replication rate after DNA damage might be controlled by the rate of RecA-coated to -uncoated singlestranded regions of DNA in the replication fork, whereas we are suggesting that uncleaved UmuD and UmuC may serve as ultimate effectors that control the rate of DNA replication by interacting with the components of the replicative DNA polymerase. Bridges has also discussed the hypothesis that a bacterium is able to actively monitor the level of DNA damage it has suffered and delay the progression of its cell cycle until the damage has been completely repaired (50). Our observations raise the interesting possibility that the ''delay'' in resumption of DNA replication is actually a timed pause rather than a pause whose lifting depends on some condition being satisfied.…”

“…From studies of mutant strains with reduced rates of excision repair both Witkin (47,48) and Bridges (49,50) have previously suggested that E. coli might delay its cell cycle to enable a certain amount of repair to occur. Bridges (50) has hypothesized that the replication rate after DNA damage might be controlled by the rate of RecA-coated to -uncoated singlestranded regions of DNA in the replication fork, whereas we are suggesting that uncleaved UmuD and UmuC may serve as ultimate effectors that control the rate of DNA replication by interacting with the components of the replicative DNA polymerase.…”

An alternative pathway of recombination of chromosomal fragments precedes recA-dependent recombination in the radioresistant bacterium Deinococcus radiodurans

“…It is accompanied by a limited amount of DNA degradation that depends on the extent of damage (for a review, see reference 21). The growth lag is dependent on the initial amount of damage and occurs in cells exposed to nonlethal (e.g., 0.5-Mrad) and partially lethal (e.g., 1.75-Mrad) DNA-damaging exposures and supports the presence of a prokaryotic checkpoint mechanism for DNA damage in D. radiodurans (2). Unlike strain MD424 cells the recA MD431 cells failed to show any further DSB mending after 1.5 h (Fig.…”

Historical overview: Searching for replication help in all of the rec places

“…A similar idea has been put forward for bacteria (83), although there are many observations that argue against a role for a checkpoint system in halting DNA replication (reviewed in ref.…”