Unwinding 20 Years of the Archaeal Minichromosome Maintenance Helicase.

Replicative DNA helicases are essential cellular enzymes that unwind duplex DNA in front of the replication fork during chromosomal DNA replication. Replicative helicases were discovered, beginning in the 1970s, in bacteria, bacteriophages, viruses, and eukarya, and, in the mid-1990s, in archaea. This year marks the 20th anniversary of the first report on the archaeal replicative helicase, the minichromosome maintenance (MCM) protein.

Do Archaea Need an Origin of Replication?

Chromosomal DNA replication starts at a specific region called an origin of replication. Until recently, all organisms were thought to require origins to replicate their chromosomes. It was recently discovered that some archaeal species do not utilize origins of replication under laboratory growth conditions.

Archaeal DNA replication.

DNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species.

Thermococcus kodakarensis DNA replication.

DNA replication plays an essential role in all life forms. Research on archaeal DNA replication began approximately 20 years ago. Progress was hindered, however, by the lack of genetic tools to supplement the biochemical and structural studies.

The archaeal DNA replication machinery: past, present and future.

Living organisms are divided into three domains: Bacteria, Archaea, and Eukarya. Whereas Bacteria and Archaea are both prokaryotes, proteins involved in information processes; replication, transcription, and translation, are more similar in Archaea and Eukarya. Here the history of the research on archaeal DNA replication is summarized and the future of the field is discussed.

The archaeal PCNA proteins.

PCNA (proliferating-cell nuclear antigen) is a ring-shaped protein that encircles duplex DNA and plays an essential role in many DNA metabolic processes. The PCNA protein interacts with a large number of cellular factors and modulates their enzymatic activities. In the present paper, we summarize the structures, functions and interactions of the archaeal PCNA proteins.

Unwinding the structure and function of the archaeal MCM helicase.

During chromosomal DNA replication, the replicative helicase unwinds the duplex DNA to provide the single-stranded DNA substrate for the polymerase. In archaea, the replicative helicase is the minichromosome maintenance (MCM) complex. The enzyme utilizes the energy of ATP hydrolysis to translocate along one strand of the duplex and unwind the complementary strand.

How is the archaeal MCM helicase assembled at the origin? Possible mechanisms.

In order for any organism to replicate its DNA, a helicase must unwind the duplex DNA in front of the replication fork. In archaea, the replicative helicase is the MCM (minichromosome maintenance) helicase. Although much is known about the biochemical properties of the MCM helicase, the mechanism of assembly at the origin of replication is unknown.

Multiple origins of replication in archaea.

Until recently, the only archaeon for which a bona fide origin of replication was reported was Pyrococcus abyssi, where a single origin was identified. Although several in silico analyses have suggested that some archaeal species might contain more than one origin, this has only been demonstrated recently. Two studies have shown that multiple origins of replication function in two archaeal species.

Archaea: an archetype for replication initiation studies?

Whereas the process of DNA replication is fundamentally conserved in the three domains of life, the archaeal system is closer to that of eukarya than bacteria. In the time since the complete genome sequences of several members of the archaeal domain became available, there has been a burst of research on archaeal DNA replication. These studies have led to both expected and surprising findings.