Hisao Masai and Ken-ichi Arai.

Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108, Japan

Received 01/17/96; Accepted 02/17/96; On-line 03/01/96

PriA-dependent replication of the E. coli chromosome (iSDR and cSDR) occurs only under specialized conditions. Especially, iSDR is specifically induced by DNA damages, and requires RecA, RecB and RecC proteins (39, 40, 41). It is hyperactivated in a recD mutant (41). These genetic requirements are extremely similar to those of adaptive (or induced) mutatgenesis which also requires the same set of recombination proteins (42, 43), which lead us to propose that iSDR is the mode of chromosomal replication, which is induced under hard environmental condition to help E. coli cells better adapt with the environment by increased mutation rate. It was previously reported that iSDR is error-prone (39). It will be important to determine whether priA is required for induced mutagenesis.

priA1::kan cells are extremely sensitive to DNA damaging agents such as UV and mytomycin C, strongly indicating that PriA protein is involved in repair of DNA damages, especially in recombination-dependent repair of double-strand breaks (DSB). Furthermore, the priA mutant exhibits decreased Hfr conjugation and decreased P1 transduction efficiency, indicating that priA is required for general homologous recombination processes. We have concluded that the phiX174-type primosome generally functions in DNA replication which is associated with recombination.

Our results indicate that the E. coli chromosome which is normally replicated by the DnaA-oriC pathway switches its replication mode to the PriA-dependent one in response to the environment (Figure 3). This temporal switch of the replication mode permits the E. coli cells to adjust to "hard life" condition in two important ways. In individual cells within the population, it will enable them to repair lesions on DNA through a recombination-dependent manner, which requires PriA-dependent DNA synthesis. It will also increase the chance of survival as a species by enhanced mutation rate caused by PriA-dependent replication. In life-cycle of bacterial cells, this sort of switch of replication modes may occur more frequently than anticipated in response to changes of the environment and similar response may also occur in eukaryotic cells (see next section).

Figure 3: Switch of replication modes in response to environmental conditions in E. coli. In E. coli, the chromosome is normally replicated by the high fidelity DnaA-dependent machinery. However, upon encountering "harsh" environment such as the presence of DNA damage-inducing agents or possibly the absence of sufficient nutrition, it is temporally switched to PriA-dependent one, which may have lower fidelity and is associated with recombination-dependent repair of DNA lesions. See text for details.