Limits...
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.

Show MeSH

Related in: MedlinePlus

The homologous recombination repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. Although the MRX complex (Mre11/Rad50/Xrs2) acts in damage recognition in this pathway, it is not shown. (Modified from Aylon and Kupiec [24].)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC1851970&req=5

Figure 2: The homologous recombination repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. Although the MRX complex (Mre11/Rad50/Xrs2) acts in damage recognition in this pathway, it is not shown. (Modified from Aylon and Kupiec [24].)

Mentions: HRR is the major form of double strand break repair utilized in yeast. A double stranded break is recognized by damage recognition proteins, and single stranded overhangs are generated at both sides of the break. A region of the genome that is homologous to the single stranded overhangs is then found. Strand invasion follows, and the homologous (non-damaged) DNA is used as a template for synthesis on the broken strand. HRR is completed through re-annealing of the broken DNA strand and ligation. See figure 2 for an overview of this process.


Stripped-down DNA repair in a highly reduced parasite.

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

The homologous recombination repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. Although the MRX complex (Mre11/Rad50/Xrs2) acts in damage recognition in this pathway, it is not shown. (Modified from Aylon and Kupiec [24].)
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: The homologous recombination repair pathway. (See text for explanation.) Blue proteins are present in E. cuniculi; all others are absent. Newly synthesized DNA is indicated in grey. Although the MRX complex (Mre11/Rad50/Xrs2) acts in damage recognition in this pathway, it is not shown. (Modified from Aylon and Kupiec [24].)
Mentions: HRR is the major form of double strand break repair utilized in yeast. A double stranded break is recognized by damage recognition proteins, and single stranded overhangs are generated at both sides of the break. A region of the genome that is homologous to the single stranded overhangs is then found. Strand invasion follows, and the homologous (non-damaged) DNA is used as a template for synthesis on the broken strand. HRR is completed through re-annealing of the broken DNA strand and ligation. See figure 2 for an overview of this process.

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