Replication and recombination in adenovirus-infected cells are temporally and functionally related

Abstract

We have studied the temporal and functional relationships between DNA replication and recombination in adenovirus-infected cells by using Southern blot hybridization to detect recombinant products among intracellular viral genomes. The data show that recombination can be detected soon after DNA replication has commenced and that the proportion of recombinant products increases thereafter. To determine the functional relationship between DNA replication and recombination, replication was blocked with the protein synthesis inhibitor anisomycin, the replication inhibitor cytosine arabinoside, and conditionally lethal mutations in either the virus-specified DNA-binding protein or the DNA polymerase. All treatments that directly or indirectly blocked DNA replication caused a delay in the appearance of recombinant products and a marked decline in their abundance relative to products of parental genotype. These data strongly suggest that DNA replication and recombination are interrelated, either because both processes share functions or because DNA structures produced by replication are suitable substrates for recombination. In addition, we have shown that some recombination function(s) is intrinsically thermolabile at 40.9°C, even in wild-type crosses, since the appearance of recombinant products is delayed and their extent is reduced compared with that from crosses performed at 39.9°C.

The essential role of yeast topoisomerase III in meiosis depends on recombination

“…The absence of Top3 in mitosis leads to the accumulation of cells with an undivided nucleus in the neck of an elongated bud (Gangloff et al ., 1994b). The associated cell cycle delay at the G 2 –M transition is consistent with an impediment of chromosome segregation, suggesting that Top3 is involved directly in the separation of replicated chromatids or, alternatively, in the resolution of topological structures resulting from either recombination during replication or collapsed replication forks (Young et al ., 1984; Kawasaki et al ., 1994; Zou and Rothstein, 1997). Because no noticeable difference in the timing of diploid spore formation could be detected when meiotic levels of recombination are abolished, we do not believe it likely that Top3 plays a meiotic‐specific role in the DNA synthesis process.…”

Herpes simplex virus type 1 alkaline nuclease is required for efficient processing of viral DNA replication intermediates

“…Second, replication and recombination appear to be functionally linked in that Sarisky and Weber showed that inversion events are mediated by the viral DNA replication machinery (50). Third, a precedent exists for a linkage between replication and recombination in other DNA viruses such as T4 (36) and adenovirus (69).…”

Cellular and adenovirus dl312 DNA metabolism in cycling or mitotic human cultures exposed to supralethal gamma radiation.

“…was UV irradiated to stimulate illegitimate recombination. This might be expected from the association of adenovirus recombination with its replication (Young et al, 1984). Apparently, d1312 DNA was a stable, inert episome in 253J cells, 549 cells, or fibroblasts.…”