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Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast.

Stepchenkova EI, Kozmin SG, Alenin VV, Pavlov YI - BMC Genet. (2005)

Bottom Line: We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA.We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP.Three of them also protect from AHA.

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Affiliation: Department of Genetics, Sankt-Petersburg State University, Sankt-Petersburg, 199034, Russia. stepchenkova@yahoo.com <stepchenkova@yahoo.com>

ABSTRACT

Background: N-hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA), are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP and related noncanonical purines in Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, and a molybdenum cofactor-dependent system. Fewer HAP-detoxification systems have been identified in yeast Saccharomyces cerevisiae and other eukaryotes. Cellular systems protecting from AHA are unknown. In the present study, we performed a genome-wide search for genes whose deletions confer sensitivity to HAP and AHA in yeast.

Results: We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA. We identified novel genes involved in the genetic control of base analogs sensitivity, including genes controlling purine metabolism, cytoskeleton organization, and amino acid metabolism.

Conclusion: We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP. Three of them also protect from AHA.

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Chemical structures of HAP and AHA and natural purine bases.
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Figure 1: Chemical structures of HAP and AHA and natural purine bases.

Mentions: Purine analogs 6-hydroxyaminopurine (HAP) and 2-amino-HAP (AHA) are powerful mutagens in bacteria, yeast, and higher eukaryotes [6,7]. It has been suggested that HAP-deoxyriboside-triphosphate (dHAPTP) is a possible endogenous contaminant of nucleotide pools under peroxyl radical stress [8]. HAP and AHA closely resemble the natural purines, hypoxanthine and xanthine (Fig. 1), and therefore, could be exploited to investigate the mechanism preventing mutations that are caused by non-canonical purine nucleotides [9-11].


Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast.

Stepchenkova EI, Kozmin SG, Alenin VV, Pavlov YI - BMC Genet. (2005)

Chemical structures of HAP and AHA and natural purine bases.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1173102&req=5

Figure 1: Chemical structures of HAP and AHA and natural purine bases.
Mentions: Purine analogs 6-hydroxyaminopurine (HAP) and 2-amino-HAP (AHA) are powerful mutagens in bacteria, yeast, and higher eukaryotes [6,7]. It has been suggested that HAP-deoxyriboside-triphosphate (dHAPTP) is a possible endogenous contaminant of nucleotide pools under peroxyl radical stress [8]. HAP and AHA closely resemble the natural purines, hypoxanthine and xanthine (Fig. 1), and therefore, could be exploited to investigate the mechanism preventing mutations that are caused by non-canonical purine nucleotides [9-11].

Bottom Line: We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA.We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP.Three of them also protect from AHA.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics, Sankt-Petersburg State University, Sankt-Petersburg, 199034, Russia. stepchenkova@yahoo.com <stepchenkova@yahoo.com>

ABSTRACT

Background: N-hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP) and 2-amino-6-hydroxylaminopurine (AHA), are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP and related noncanonical purines in Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, and a molybdenum cofactor-dependent system. Fewer HAP-detoxification systems have been identified in yeast Saccharomyces cerevisiae and other eukaryotes. Cellular systems protecting from AHA are unknown. In the present study, we performed a genome-wide search for genes whose deletions confer sensitivity to HAP and AHA in yeast.

Results: We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA. We identified novel genes involved in the genetic control of base analogs sensitivity, including genes controlling purine metabolism, cytoskeleton organization, and amino acid metabolism.

Conclusion: We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP. Three of them also protect from AHA.

Show MeSH
Related in: MedlinePlus