APT1
 , but Not
 APT2
 , Codes for a Functional Adenine Phosphoribosyltransferase in
 Saccharomyces cerevisiae

Alfonzo, Juan D.; Crother, Timothy R.; Guetsova, Maria L.; Daignan‐Fornier, Bertrand; Taylor, Milton W.

doi:10.1128/jb.181.1.347-352.1999

Cited by 19 publications

(13 citation statements)

References 31 publications

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“…A third resistance mechanism is to interfere with activation of the drug, and it is possible that APT2 could act in this way. Our finding that APT2 overexpression confers resistance to HAP is surprising since previous studies did not detect a knockout phenotype or enzymatic activity associated with APT2 , which was therefore proposed to be a pseudogene [ 37 ]. The homology to APT1 which encodes APRT suggests that APT2 , if active, should encode an enzyme with similar activity.…”

Section: Discussionmentioning

confidence: 73%

“…However, Apt2p lacks APRT activity when expressed in E . coli and a disruption of the APT2 gene has no apparent phenotype in yeast [ 37 ]. It is thus not clear what enzymatic activity, if any, that Atp2p possesses.…”

Section: Resultsmentioning

confidence: 99%

“…One possible explanation for our finding that overexpression of APT2 confers resistance to HAP could be that it interferes with the expression of Apt1p and thus with its ability to activate HAP. Such interference could occur by promoter competition for an activator of both genes, since APT2 is known to be transcribed [ 37 ]. Alternatively, since APRT is a dimeric enzyme [ 37 ], overexpression of APT2 might lead to the formation of inactive Apt1p-Apt2p heterodimers.…”

Section: Discussionmentioning

confidence: 99%

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Gene dosage effects in yeast support broader roles for the LOG1, HAM1 and DUT1 genes in detoxification of nucleotide analogues

Carlsson

Ronne

2018

PLoS ONE

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Purine and pyrimidine analogues have important uses in chemotherapies against cancer, and a better understanding of the mechanisms that cause resistance to these drugs is therefore of importance in cancer treatment. In the yeast Saccharomyces cerevisiae, overexpression of the HAM1 gene encoding inosine triphosphate pyrophosphatase confers resistance to both the purine analogue 6-N-hydroxylaminopurine (HAP) and the pyrimidine analogue 5-fluorouracil (5-FU) (Carlsson et al., 2013, PLoS One 8, e52094). To find out more about the mechanisms of resistance to nucleotide analogues, and possible interdependencies between purine and pyrimidine analogue resistance mechanisms, we screened a plasmid library in yeast for genes that confer HAP resistance when overexpressed. We cloned four such genes: ADE4, DUT1, APT2, and ATR1. We further looked for genetic interactions between these genes and genes previously found to confer resistance to 5-FU. We found that HMS1, LOG1 (YJL055W), HAM1, and ATR1 confer resistance to both 5-FU and HAP, whereas ADE4, DUT1 and APT2 are specific for HAP resistance, and CPA1 and CPA2 specific for 5-FU resistance. Possible mechanisms for 5-FU and HAP detoxification are discussed based on the observed genetic interactions. Based on the effect of LOG1 against both 5-FU and HAP toxicity, we propose that the original function of the LOG (LONELY GUY) family of proteins likely was to degrade non-canonical nucleotides, and that their role in cytokinin production is a later development in some organisms.

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Section: Discussionmentioning

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gene dosage effects in yeast support broader roles for the LOG1, HAM1 and DUT1 genes in detoxification of nucleotide analogues

Carlsson

Ronne

2018

PLoS ONE

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“…4A). This level of inhibition of TBSV repRNA accumulation might not be significant, because over-expression of a pseudogene (APT2), which has no enzymatic activity when expressed (Alfonzo et al, 1999), also led to reduced TBSV repRNA accumulation (63.7 ± 15.9%), suggesting that two-fold or less reduction might be due to the reduced ability of yeast cells to support repRNA accumulation under the protein over-expression condition. Together, the above experiments indicated that over-expression of 40% of the 45 RNA-binding host proteins could affect TBSV repRNA accumulation in yeast.…”

Section: Effect Of Over-expression Of Selected Host Proteins On Tbsv mentioning

confidence: 99%

Translation elongation factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor

Li¹,

Pogany²,

Panavas³

et al. 2009

Virology

122

181

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Host RNA-binding proteins are likely to play multiple, integral roles during replication of plus-strand RNA viruses. To identify host proteins that bind to viral RNAs, we took a global approach based on the yeast proteome microarray, which contains 4080 purified yeast proteins. The biotin-labeled RNA probes included two distantly related RNA viruses, namely Tomato bushy stunt virus (TBSV) and Brome mosaic virus (BMV). Altogether, we have identified 57 yeast proteins that bound to TBSV RNA and/or BMV RNA. Among the identified host proteins, eleven bound to TBSV RNA and seven bound to BMV RNA with high selectivity, whereas the remaining 39 host proteins bound to both viral RNAs. The interaction between the TBSV replicon RNA and five of the identified host proteins were confirmed via gel-mobility shift and co-purification experiments from yeast. Over-expression of the host proteins in yeast, a model host for TBSV, revealed that 4 host proteins that enhanced TBSV replication as well as 14 proteins that inhibited replication. Detailed analysis of one of the identified yeast proteins binding to TBSV RNA, namely translation elongation factor eEF1A, revealed that it is present in the highly purified tombusvirus replicase complex. We also demonstrate binding of eEF1A to the p33 replication protein and a known cis-acting element at the 3′ end of TBSV RNA. Using a functional mutant of eEF1A, we provide evidence on the involvement of eEF1A in TBSV replication.

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“…Mutations affecting adenine phosphoribosyl transferase (APRT) and hypoxanthine-guanine phosphoribosyl transferase (HGPRT) in S. cerevisiae have been described previously (10,12,13). APRT is encoded by the APT1 gene (2), while APT2, a gene encoding a putative PRT highly similar to Apt1p, has been reported (14), although no enzymatic activity could be associated with this protein (1). HGPRT is encoded by the HPT1 gene (6).…”

mentioning

confidence: 99%

Isolation and Characterization of the Saccharomyces cerevisiae XPT1 Gene Encoding Xanthine Phosphoribosyl Transferase

et al. 1999

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APT1 , but Not APT2 , Codes for a Functional Adenine Phosphoribosyltransferase in Saccharomyces cerevisiae

Cited by 19 publications

References 31 publications

Gene dosage effects in yeast support broader roles for the LOG1, HAM1 and DUT1 genes in detoxification of nucleotide analogues

Gene dosage effects in yeast support broader roles for the LOG1, HAM1 and DUT1 genes in detoxification of nucleotide analogues

Translation elongation factor 1A is a component of the tombusvirus replicase complex and affects the stability of the p33 replication co-factor

Isolation and Characterization of the Saccharomyces cerevisiae XPT1 Gene Encoding Xanthine Phosphoribosyl Transferase

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