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Classification and evolutionary history of the single-strand annealing proteins, RecT, Redbeta, ERF and RAD52.

Iyer LM, Koonin EV, Aravind L - BMC Genomics (2002)

Bottom Line: There are three evolutionarily distinct superfamilies of SSAPs, namely the RecT/Redbeta, ERF, and RAD52, that have different sequence conservation patterns and predicted folds.All these SSAPs appear to be primarily of bacteriophage origin and have been acquired by numerous phylogenetically distant cellular genomes.They generally occur in predicted operons encoding one or more of a set of conserved DNA recombination proteins that appear to be the principal functional partners of the SSAPs.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. lakshmin@ncbi.nlm.nih.gov

ABSTRACT

Background: The DNA single-strand annealing proteins (SSAPs), such as RecT, Redbeta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. Recently, they have been shown to form similar helical quaternary superstructures. However, despite the functional similarities between these diverse SSAPs, their actual evolutionary affinities are poorly understood.

Results: Using sensitive computational sequence analysis, we show that the RecT and Redbeta proteins, along with several other bacterial proteins, form a distinct superfamily. The ERF and Rad52 families show no direct evolutionary relationship to these proteins and define novel superfamilies of their own. We identify several previously unknown members of each of these superfamilies and also report, for the first time, bacterial and viral homologs of Rad52. Additionally, we predict the presence of aberrant HhH modules in RAD52 that are likely to be involved in DNA-binding. Using the contextual information obtained from the analysis of gene neighborhoods, we provide evidence of the interaction of the bacterial members of each of these SSAP superfamilies with a similar set of DNA repair/recombination protein. These include different nucleases or Holliday junction resolvases, the ABC ATPase SbcC and the single-strand-binding protein. We also present evidence of independent assembly of some of the predicted operons encoding SSAPs and in situ displacement of functionally similar genes.

Conclusions: There are three evolutionarily distinct superfamilies of SSAPs, namely the RecT/Redbeta, ERF, and RAD52, that have different sequence conservation patterns and predicted folds. All these SSAPs appear to be primarily of bacteriophage origin and have been acquired by numerous phylogenetically distant cellular genomes. They generally occur in predicted operons encoding one or more of a set of conserved DNA recombination proteins that appear to be the principal functional partners of the SSAPs.

No MeSH data available.


Multiple sequence alignment of the RAD52 protein superfamily. The coloring reflects the consensus at 90% conservation. The coloring scheme and secondary structure assignment abbreviations are as in Fig. 1. Species abbreviations are as follows: BPul36: Bacteriophage ul36. Cab: Clostridium acetobutylicum, Dr: Deinococcus radiodurans, Hs: Homo sapiens, Kla: Kluyveromyces lactis, NC: Neurospora crassa, Sc: Saccharomyces cerevisiae, Sp: Schizosaccharomyces pombe, Sparatyphi: Salmonella paratyphi A, Ralbus: Ruminococcus albus. The Shiga toxin-converting phage RAD52-like protein (gi: 17977996) is nearly identical to the Salmonella paratyphi A RAD52 like protein. The RAD52-like proteins from Bacteriophage ul36 (gi: 8248159) and Ruminococcus albus are respectively adjacent to genes encoding the single-strand binding protein and the λ-type exonuclease.
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Figure 5: Multiple sequence alignment of the RAD52 protein superfamily. The coloring reflects the consensus at 90% conservation. The coloring scheme and secondary structure assignment abbreviations are as in Fig. 1. Species abbreviations are as follows: BPul36: Bacteriophage ul36. Cab: Clostridium acetobutylicum, Dr: Deinococcus radiodurans, Hs: Homo sapiens, Kla: Kluyveromyces lactis, NC: Neurospora crassa, Sc: Saccharomyces cerevisiae, Sp: Schizosaccharomyces pombe, Sparatyphi: Salmonella paratyphi A, Ralbus: Ruminococcus albus. The Shiga toxin-converting phage RAD52-like protein (gi: 17977996) is nearly identical to the Salmonella paratyphi A RAD52 like protein. The RAD52-like proteins from Bacteriophage ul36 (gi: 8248159) and Ruminococcus albus are respectively adjacent to genes encoding the single-strand binding protein and the λ-type exonuclease.

Mentions: The baker's yeast protein RAD52 and its paralog RAD59 define a small family of proteins thus far represented in fungi, vertebrates and the early-branching ameboid eukaryote, Entamoeba histolytica. Rad52 functions in conjunction with the RecA ortholog, the RAD51 recombinase in double-strand break repair and meiotic recombination [6]. RAD52 binds ssDNA during recombination and also shows a quaternary organization similar to those of RecT/Redβ and ERF [16,26]. However, RAD52-like proteins showed no detectable sequence similarity with either the ERF or the RecT/Redβ-like proteins. Sequence searches initiated with the conserved globular region of the eukaryotic RAD52 proteins readily detected their homologs from other eukaryotes and, at convergence, also retrieved from the database certain bacterial proteins, such as DR0423 from Deinococcus and CAC1936 from Clostridium respectively, with border-like statistical significance (e ~ .05). These bacterial proteins form a small family that is additionally represented in Salmonella paratyphi A, the temperate bacteriophage u136 of Lactococcus lactis (ORF252-encoded protein) and a Shiga toxin-converting phage from E. coli. Iterative profile searches initiated with CAC1936 from Clostridium acetobutylicum and its S. paratyphi A ortholog correspondingly retrieved S. cerevisiae RAD52 and its eukaryotic homologs, with borderline e-values at convergence (~0.043). The alignment between these bacterial proteins and the eukaryotic Rad52 homologs was co-linear throughout the entire length of their shared globular region and the Gibbs sampling procedure detected two motifs of greater than 20 residues, with a probability of chance occurrence in these proteins less than 10-18 (Fig. 5). In addition to the similar conservation pattern, separate secondary structure predictions for both the eukaryotic RAD52 family and their potential bacterial homologs showed a complete concordance of the predicted structural elements between RAD52 and the bacterial proteins, strongly suggesting that they all belong to a single homologous superfamily (hereinafter the RAD52 superfamily).


Classification and evolutionary history of the single-strand annealing proteins, RecT, Redbeta, ERF and RAD52.

Iyer LM, Koonin EV, Aravind L - BMC Genomics (2002)

Multiple sequence alignment of the RAD52 protein superfamily. The coloring reflects the consensus at 90% conservation. The coloring scheme and secondary structure assignment abbreviations are as in Fig. 1. Species abbreviations are as follows: BPul36: Bacteriophage ul36. Cab: Clostridium acetobutylicum, Dr: Deinococcus radiodurans, Hs: Homo sapiens, Kla: Kluyveromyces lactis, NC: Neurospora crassa, Sc: Saccharomyces cerevisiae, Sp: Schizosaccharomyces pombe, Sparatyphi: Salmonella paratyphi A, Ralbus: Ruminococcus albus. The Shiga toxin-converting phage RAD52-like protein (gi: 17977996) is nearly identical to the Salmonella paratyphi A RAD52 like protein. The RAD52-like proteins from Bacteriophage ul36 (gi: 8248159) and Ruminococcus albus are respectively adjacent to genes encoding the single-strand binding protein and the λ-type exonuclease.
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Related In: Results  -  Collection

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Figure 5: Multiple sequence alignment of the RAD52 protein superfamily. The coloring reflects the consensus at 90% conservation. The coloring scheme and secondary structure assignment abbreviations are as in Fig. 1. Species abbreviations are as follows: BPul36: Bacteriophage ul36. Cab: Clostridium acetobutylicum, Dr: Deinococcus radiodurans, Hs: Homo sapiens, Kla: Kluyveromyces lactis, NC: Neurospora crassa, Sc: Saccharomyces cerevisiae, Sp: Schizosaccharomyces pombe, Sparatyphi: Salmonella paratyphi A, Ralbus: Ruminococcus albus. The Shiga toxin-converting phage RAD52-like protein (gi: 17977996) is nearly identical to the Salmonella paratyphi A RAD52 like protein. The RAD52-like proteins from Bacteriophage ul36 (gi: 8248159) and Ruminococcus albus are respectively adjacent to genes encoding the single-strand binding protein and the λ-type exonuclease.
Mentions: The baker's yeast protein RAD52 and its paralog RAD59 define a small family of proteins thus far represented in fungi, vertebrates and the early-branching ameboid eukaryote, Entamoeba histolytica. Rad52 functions in conjunction with the RecA ortholog, the RAD51 recombinase in double-strand break repair and meiotic recombination [6]. RAD52 binds ssDNA during recombination and also shows a quaternary organization similar to those of RecT/Redβ and ERF [16,26]. However, RAD52-like proteins showed no detectable sequence similarity with either the ERF or the RecT/Redβ-like proteins. Sequence searches initiated with the conserved globular region of the eukaryotic RAD52 proteins readily detected their homologs from other eukaryotes and, at convergence, also retrieved from the database certain bacterial proteins, such as DR0423 from Deinococcus and CAC1936 from Clostridium respectively, with border-like statistical significance (e ~ .05). These bacterial proteins form a small family that is additionally represented in Salmonella paratyphi A, the temperate bacteriophage u136 of Lactococcus lactis (ORF252-encoded protein) and a Shiga toxin-converting phage from E. coli. Iterative profile searches initiated with CAC1936 from Clostridium acetobutylicum and its S. paratyphi A ortholog correspondingly retrieved S. cerevisiae RAD52 and its eukaryotic homologs, with borderline e-values at convergence (~0.043). The alignment between these bacterial proteins and the eukaryotic Rad52 homologs was co-linear throughout the entire length of their shared globular region and the Gibbs sampling procedure detected two motifs of greater than 20 residues, with a probability of chance occurrence in these proteins less than 10-18 (Fig. 5). In addition to the similar conservation pattern, separate secondary structure predictions for both the eukaryotic RAD52 family and their potential bacterial homologs showed a complete concordance of the predicted structural elements between RAD52 and the bacterial proteins, strongly suggesting that they all belong to a single homologous superfamily (hereinafter the RAD52 superfamily).

Bottom Line: There are three evolutionarily distinct superfamilies of SSAPs, namely the RecT/Redbeta, ERF, and RAD52, that have different sequence conservation patterns and predicted folds.All these SSAPs appear to be primarily of bacteriophage origin and have been acquired by numerous phylogenetically distant cellular genomes.They generally occur in predicted operons encoding one or more of a set of conserved DNA recombination proteins that appear to be the principal functional partners of the SSAPs.

View Article: PubMed Central - HTML - PubMed

Affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA. lakshmin@ncbi.nlm.nih.gov

ABSTRACT

Background: The DNA single-strand annealing proteins (SSAPs), such as RecT, Redbeta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. Recently, they have been shown to form similar helical quaternary superstructures. However, despite the functional similarities between these diverse SSAPs, their actual evolutionary affinities are poorly understood.

Results: Using sensitive computational sequence analysis, we show that the RecT and Redbeta proteins, along with several other bacterial proteins, form a distinct superfamily. The ERF and Rad52 families show no direct evolutionary relationship to these proteins and define novel superfamilies of their own. We identify several previously unknown members of each of these superfamilies and also report, for the first time, bacterial and viral homologs of Rad52. Additionally, we predict the presence of aberrant HhH modules in RAD52 that are likely to be involved in DNA-binding. Using the contextual information obtained from the analysis of gene neighborhoods, we provide evidence of the interaction of the bacterial members of each of these SSAP superfamilies with a similar set of DNA repair/recombination protein. These include different nucleases or Holliday junction resolvases, the ABC ATPase SbcC and the single-strand-binding protein. We also present evidence of independent assembly of some of the predicted operons encoding SSAPs and in situ displacement of functionally similar genes.

Conclusions: There are three evolutionarily distinct superfamilies of SSAPs, namely the RecT/Redbeta, ERF, and RAD52, that have different sequence conservation patterns and predicted folds. All these SSAPs appear to be primarily of bacteriophage origin and have been acquired by numerous phylogenetically distant cellular genomes. They generally occur in predicted operons encoding one or more of a set of conserved DNA recombination proteins that appear to be the principal functional partners of the SSAPs.

No MeSH data available.