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Stripped-down DNA repair in a highly reduced parasite.

Gill EE, Fast NM - BMC Mol. Biol. (2007)

Bottom Line: Some of these organisms, including E. cuniculi, also have uniquely small genomes that are within the prokaryotic range.A loss of these mechanisms invariably results in accumulation of mutations and/or cell death.All of these genes are relatively well conserved within eukaryotes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Botany, University of British Columbia, Vancouver, British Columbia, Canada. egill@interchange.ubc.ca

ABSTRACT

Background: Encephalitozoon cuniculi is a member of a distinctive group of single-celled parasitic eukaryotes called microsporidia, which are closely related to fungi. Some of these organisms, including E. cuniculi, also have uniquely small genomes that are within the prokaryotic range. Thus, E. cuniculi has undergone a massive genome reduction which has resulted in a loss of genes from diverse biological pathways, including those that act in DNA repair.DNA repair is essential to any living cell. A loss of these mechanisms invariably results in accumulation of mutations and/or cell death. Six major pathways of DNA repair in eukaryotes include: non-homologous end joining (NHEJ), homologous recombination repair (HRR), mismatch repair (MMR), nucleotide excision repair (NER), base excision repair (BER) and methyltransferase repair. DNA polymerases are also critical players in DNA repair processes. Given the close relationship between microsporidia and fungi, the repair mechanisms present in E. cuniculi were compared to those of the yeast Saccharomyces cerevisiae to ascertain how the process of genome reduction has affected the DNA repair pathways.

Results: E. cuniculi lacks 16 (plus another 6 potential absences) of the 56 DNA repair genes sought via BLASTP and PSI-BLAST searches. Six of 14 DNA polymerases or polymerase subunits are also absent in E. cuniculi. All of these genes are relatively well conserved within eukaryotes. The absence of genes is not distributed equally among the different repair pathways; some pathways lack only one protein, while there is a striking absence of many proteins that are components of both double strand break repair pathways. All specialized repair polymerases are also absent.

Conclusion: Given the large number of DNA repair genes that are absent from the double strand break repair pathways, E. cuniculi is a prime candidate for the study of double strand break repair with minimal machinery. Strikingly, all of the double strand break repair genes that have been retained by E. cuniculi participate in other biological pathways.

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The non-homologous end joining repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. (Modified from Hefferin and Tomkinson [32].)
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Figure 3: The non-homologous end joining repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. (Modified from Hefferin and Tomkinson [32].)

Mentions: The NHEJ process begins when the Ku complex (Ku70/Ku80) binds either end of the double strand break (See Fig 3). These proteins are DNA-dependent protein kinases that also have a role in telomere maintenance. Once bound to the damaged site, the Ku complex is responsible for recruiting the MRX complex for the next stage in the repair process. The MRX complex is composed of Rad50 (an ATP binding protein), Mre11 (a 5'-3' exonuclease) and Xrs2 (responsible for aligning the MRX complex with the break site) [31]. Dnl4/Lif1 (a DNA ligase complex) is tethered to the break site by Xrs2 and the Ku complex. The DNA polymerase Pol4 and the structure-specific nuclease Rad27 are the last players to arrive at the scene, thus completing the repair complex.


Stripped-down DNA repair in a highly reduced parasite.

Gill EE, Fast NM - BMC Mol. Biol. (2007)

The non-homologous end joining repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. (Modified from Hefferin and Tomkinson [32].)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1851970&req=5

Figure 3: The non-homologous end joining repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. (Modified from Hefferin and Tomkinson [32].)
Mentions: The NHEJ process begins when the Ku complex (Ku70/Ku80) binds either end of the double strand break (See Fig 3). These proteins are DNA-dependent protein kinases that also have a role in telomere maintenance. Once bound to the damaged site, the Ku complex is responsible for recruiting the MRX complex for the next stage in the repair process. The MRX complex is composed of Rad50 (an ATP binding protein), Mre11 (a 5'-3' exonuclease) and Xrs2 (responsible for aligning the MRX complex with the break site) [31]. Dnl4/Lif1 (a DNA ligase complex) is tethered to the break site by Xrs2 and the Ku complex. The DNA polymerase Pol4 and the structure-specific nuclease Rad27 are the last players to arrive at the scene, thus completing the repair complex.

Bottom Line: Some of these organisms, including E. cuniculi, also have uniquely small genomes that are within the prokaryotic range.A loss of these mechanisms invariably results in accumulation of mutations and/or cell death.All of these genes are relatively well conserved within eukaryotes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Botany, University of British Columbia, Vancouver, British Columbia, Canada. egill@interchange.ubc.ca

ABSTRACT

Background: Encephalitozoon cuniculi is a member of a distinctive group of single-celled parasitic eukaryotes called microsporidia, which are closely related to fungi. Some of these organisms, including E. cuniculi, also have uniquely small genomes that are within the prokaryotic range. Thus, E. cuniculi has undergone a massive genome reduction which has resulted in a loss of genes from diverse biological pathways, including those that act in DNA repair.DNA repair is essential to any living cell. A loss of these mechanisms invariably results in accumulation of mutations and/or cell death. Six major pathways of DNA repair in eukaryotes include: non-homologous end joining (NHEJ), homologous recombination repair (HRR), mismatch repair (MMR), nucleotide excision repair (NER), base excision repair (BER) and methyltransferase repair. DNA polymerases are also critical players in DNA repair processes. Given the close relationship between microsporidia and fungi, the repair mechanisms present in E. cuniculi were compared to those of the yeast Saccharomyces cerevisiae to ascertain how the process of genome reduction has affected the DNA repair pathways.

Results: E. cuniculi lacks 16 (plus another 6 potential absences) of the 56 DNA repair genes sought via BLASTP and PSI-BLAST searches. Six of 14 DNA polymerases or polymerase subunits are also absent in E. cuniculi. All of these genes are relatively well conserved within eukaryotes. The absence of genes is not distributed equally among the different repair pathways; some pathways lack only one protein, while there is a striking absence of many proteins that are components of both double strand break repair pathways. All specialized repair polymerases are also absent.

Conclusion: Given the large number of DNA repair genes that are absent from the double strand break repair pathways, E. cuniculi is a prime candidate for the study of double strand break repair with minimal machinery. Strikingly, all of the double strand break repair genes that have been retained by E. cuniculi participate in other biological pathways.

Show MeSH
Related in: MedlinePlus