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Genomic context analysis in Archaea suggests previously unrecognized links between DNA replication and translation.

Berthon J, Cortez D, Forterre P - Genome Biol. (2008)

Bottom Line: The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis.Our genome context analysis suggests specific functional interactions for proteins involved in DNA replication between each other or with proteins involved in DNA repair or transcription.Furthermore, it suggests a previously unrecognized regulatory network coupling DNA replication and translation in Archaea that may also exist in Eukarya.

View Article: PubMed Central - HTML - PubMed

Affiliation: Univ. Paris-Sud 11, CNRS, UMR8621, Institut de Génétique et Microbiologie, 91405 Orsay CEDEX, France. jonathan.berthon@igmors.u-psud.fr

ABSTRACT

Background: Comparative analysis of genomes is valuable to explore evolution of genomes, deduce gene functions, or predict functional linking between proteins. Here, we have systematically analyzed the genomic environment of all known DNA replication genes in 27 archaeal genomes to infer new connections for DNA replication proteins from conserved genomic associations.

Results: Two distinct sets of DNA replication genes frequently co-localize in archaeal genomes: the first includes the genes for PCNA, the small subunit of the DNA primase (PriS), and Gins15; the second comprises the genes for MCM and Gins23. Other genomic associations of genes encoding proteins involved in informational processes that may be functionally relevant at the cellular level have also been noted; in particular, the association between the genes for PCNA, transcription factor S, and NudF. Surprisingly, a conserved cluster of genes coding for proteins involved in translation or ribosome biogenesis (S27E, L44E, aIF-2 alpha, Nop10) is almost systematically contiguous to the group of genes coding for PCNA, PriS, and Gins15. The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis. Interestingly, the gene encoding the S27E protein, also known as metallopanstimulin 1 (MPS-1) in human, is overexpressed in multiple cancer cell lines.

Conclusion: Our genome context analysis suggests specific functional interactions for proteins involved in DNA replication between each other or with proteins involved in DNA repair or transcription. Furthermore, it suggests a previously unrecognized regulatory network coupling DNA replication and translation in Archaea that may also exist in Eukarya.

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Replication origin is adjacent to cdc6, and close to gene for DP1 in several euryarchaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). The origins of replication (oriC) are shown as bubble-shaped replication intermediate sketches; solid lines are used when the origin has been identified experimentally, and broken lines are used when the origin has been predicted with in silico analyses. Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.
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Figure 3: Replication origin is adjacent to cdc6, and close to gene for DP1 in several euryarchaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). The origins of replication (oriC) are shown as bubble-shaped replication intermediate sketches; solid lines are used when the origin has been identified experimentally, and broken lines are used when the origin has been predicted with in silico analyses. Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.

Mentions: Besides the DNA replication genes that belong to the PPsG cluster, the gene that co-localizes more frequently with other DNA replication genes is cdc6. Our analysis suggests a loose connection between the initiator protein Cdc6 and the clamp loader RFC, the helicase MCM and DNA polymerases (either B or D), respectively. Hence, the gene encoding Cdc6 is located in the vicinity of the genes encoding RFC-s1 and RFC-l in P. aerophilum; RFC-s in H. salinarum; MCM and DP2 in M. maripaludis; and DP1 in H. salinarum, H. marismortui, Methanothermobacter thermautotrophicus, and Methanosphaera stadtmanae (Additional data file 2). Remarkably, all these proteins should be recruited at the replication origin for the initiation of DNA replication. In addition, the genes that are located in the vicinity of the cdc6 gene in the genomes of P. aerophilum, Halobacteria and methanogens correspond to those that form the replication islands of Pyrococcus or Sulfolobus (Additional data file 2). Since the gene encoding Cdc6 is frequently associated with a predicted replication origin [22,23,47], co-localization of the cdc6 gene with various DNA replication genes in the vicinity of oriC could help the recruitment of DNA replication proteins to build new DNA replication factories at the origin of replication. Among the various gene associations of cdc6 with other DNA replication genes, the most recurrent is the linkage with the gene encoding the small subunit of PolD. First noticed in M. thermautotrophicus, P. furiosus and P. horikoshii [48], this association turns out to be conserved in all Thermococcales, Halobacteriales, and Methanosarcinales (Figure 3), suggesting that PolD may be recruited by Cdc6 to oriC via its small subunit DP1. Interestingly, we recently noticed the presence of an origin recognition box (ORB) and mini-ORB repeats in the gene encoding the DP1 subunit of the four Thermococcales [49]. This suggests that the small subunit of PolD indeed plays a specific role, which remains to be explored in the initiation of DNA replication in Euryarchaeota.


Genomic context analysis in Archaea suggests previously unrecognized links between DNA replication and translation.

Berthon J, Cortez D, Forterre P - Genome Biol. (2008)

Replication origin is adjacent to cdc6, and close to gene for DP1 in several euryarchaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). The origins of replication (oriC) are shown as bubble-shaped replication intermediate sketches; solid lines are used when the origin has been identified experimentally, and broken lines are used when the origin has been predicted with in silico analyses. Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2643942&req=5

Figure 3: Replication origin is adjacent to cdc6, and close to gene for DP1 in several euryarchaeal genomes. Orthologous genes are indicated in the same color. Each gene is denoted by the name of the protein it encodes (see the key at the bottom). The origins of replication (oriC) are shown as bubble-shaped replication intermediate sketches; solid lines are used when the origin has been identified experimentally, and broken lines are used when the origin has been predicted with in silico analyses. Species or cell lineages that have the same genomic environment are listed and the number of corresponding genomes is given in parentheses. White arrows correspond to additional functionally unrelated genes. Genes are not shown to scale.
Mentions: Besides the DNA replication genes that belong to the PPsG cluster, the gene that co-localizes more frequently with other DNA replication genes is cdc6. Our analysis suggests a loose connection between the initiator protein Cdc6 and the clamp loader RFC, the helicase MCM and DNA polymerases (either B or D), respectively. Hence, the gene encoding Cdc6 is located in the vicinity of the genes encoding RFC-s1 and RFC-l in P. aerophilum; RFC-s in H. salinarum; MCM and DP2 in M. maripaludis; and DP1 in H. salinarum, H. marismortui, Methanothermobacter thermautotrophicus, and Methanosphaera stadtmanae (Additional data file 2). Remarkably, all these proteins should be recruited at the replication origin for the initiation of DNA replication. In addition, the genes that are located in the vicinity of the cdc6 gene in the genomes of P. aerophilum, Halobacteria and methanogens correspond to those that form the replication islands of Pyrococcus or Sulfolobus (Additional data file 2). Since the gene encoding Cdc6 is frequently associated with a predicted replication origin [22,23,47], co-localization of the cdc6 gene with various DNA replication genes in the vicinity of oriC could help the recruitment of DNA replication proteins to build new DNA replication factories at the origin of replication. Among the various gene associations of cdc6 with other DNA replication genes, the most recurrent is the linkage with the gene encoding the small subunit of PolD. First noticed in M. thermautotrophicus, P. furiosus and P. horikoshii [48], this association turns out to be conserved in all Thermococcales, Halobacteriales, and Methanosarcinales (Figure 3), suggesting that PolD may be recruited by Cdc6 to oriC via its small subunit DP1. Interestingly, we recently noticed the presence of an origin recognition box (ORB) and mini-ORB repeats in the gene encoding the DP1 subunit of the four Thermococcales [49]. This suggests that the small subunit of PolD indeed plays a specific role, which remains to be explored in the initiation of DNA replication in Euryarchaeota.

Bottom Line: The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis.Our genome context analysis suggests specific functional interactions for proteins involved in DNA replication between each other or with proteins involved in DNA repair or transcription.Furthermore, it suggests a previously unrecognized regulatory network coupling DNA replication and translation in Archaea that may also exist in Eukarya.

View Article: PubMed Central - HTML - PubMed

Affiliation: Univ. Paris-Sud 11, CNRS, UMR8621, Institut de Génétique et Microbiologie, 91405 Orsay CEDEX, France. jonathan.berthon@igmors.u-psud.fr

ABSTRACT

Background: Comparative analysis of genomes is valuable to explore evolution of genomes, deduce gene functions, or predict functional linking between proteins. Here, we have systematically analyzed the genomic environment of all known DNA replication genes in 27 archaeal genomes to infer new connections for DNA replication proteins from conserved genomic associations.

Results: Two distinct sets of DNA replication genes frequently co-localize in archaeal genomes: the first includes the genes for PCNA, the small subunit of the DNA primase (PriS), and Gins15; the second comprises the genes for MCM and Gins23. Other genomic associations of genes encoding proteins involved in informational processes that may be functionally relevant at the cellular level have also been noted; in particular, the association between the genes for PCNA, transcription factor S, and NudF. Surprisingly, a conserved cluster of genes coding for proteins involved in translation or ribosome biogenesis (S27E, L44E, aIF-2 alpha, Nop10) is almost systematically contiguous to the group of genes coding for PCNA, PriS, and Gins15. The functional relevance of this cluster encoding proteins conserved in Archaea and Eukarya is strongly supported by statistical analysis. Interestingly, the gene encoding the S27E protein, also known as metallopanstimulin 1 (MPS-1) in human, is overexpressed in multiple cancer cell lines.

Conclusion: Our genome context analysis suggests specific functional interactions for proteins involved in DNA replication between each other or with proteins involved in DNA repair or transcription. Furthermore, it suggests a previously unrecognized regulatory network coupling DNA replication and translation in Archaea that may also exist in Eukarya.

Show MeSH
Related in: MedlinePlus