The N-terminal region of the Schizosaccharomyces pombe RecQ helicase, Rqh1p, physically interacts with Topoisomerase III and is required for Rqh1p function

Ahmad, Fouzia; Stewart, Elspeth

doi:10.1007/s00438-005-1111-3

Cited by 28 publications

(18 citation statements)

References 50 publications

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“…Cells were incubated as described for panel A. pot1⌬ rqh1-hd top3⌬ triple mutant is lethal but is suppressed by deletion of rad51 ؉ . Rqh1 binds to type 3 topoisomerase (Top3) and functions as a Rqh1-Top3-Rmi1 complex (34,35). We asked whether Top3 was also required for the viability of pot1⌬ cells and, if so, whether this requirement was also canceled by the deletion of rad51 ϩ .…”

Section: Resultsmentioning

confidence: 99%

“…We asked whether Top3 was also required for the viability of pot1⌬ cells and, if so, whether this requirement was also canceled by the deletion of rad51 ϩ . The top3 disruptant is lethal, but this lethality can be suppressed by a deletion or mutation of rqh1 ϩ (34,36). We used a top3 disruptant in an rqh1-hd mutant background because both the pot1⌬ rqh1-hd and top3⌬ rqh1-hd double mutants are viable, which enabled us to test whether the pot1⌬ rqh1-hd top3⌬ triple mutant was viable (32,37).…”

Section: Resultsmentioning

confidence: 99%

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Fission Yeast RecQ Helicase Rqh1 Is Required for the Maintenance of Circular Chromosomes

Nanbu

Takahashi

Murray

et al. 2013

Molecular and Cellular Biology

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c Protection of telomeres protein 1 (Pot1) binds to single-stranded telomere overhangs and protects chromosome ends. RecQ helicases regulate homologous recombination at multiple stages, including resection, strand displacement, and resolution. Fission yeast pot1 and RecQ helicase rqh1 double mutants are synthetically lethal, but the mechanism is not fully understood. Here, we show that the synthetic lethality of pot1⌬ rqh1⌬ double mutants is due to inappropriate homologous recombination, as it is suppressed by the deletion of rad51 ؉ . The expression of Rad51 in the pot1⌬ rqh1⌬ rad51⌬ triple mutant, which has circular chromosomes, is lethal. Reduction of the expression of Rqh1 in a pot1 disruptant with circular chromosomes caused chromosome missegregation, and this defect was partially suppressed by the deletion of rad51 ؉ . Taken together, our results suggest that Rqh1 is required for the maintenance of circular chromosomes when homologous recombination is active. Crossovers between circular monomeric chromosomes generate dimers that cannot segregate properly in Escherichia coli. We propose that Rqh1 inhibits crossovers between circular monomeric chromosomes to suppress the generation of circular dimers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Fission Yeast RecQ Helicase Rqh1 Is Required for the Maintenance of Circular Chromosomes

Nanbu

Takahashi

Murray

et al. 2013

Molecular and Cellular Biology

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“…However, mutations affecting budding yeast Top3, the topoisomerase IIIa ortholog, have phenotypes similar to those of sgs1 mutants, supporting a DNA processing pathway involving both proteins rather than Sgs1 alone (Ira et al 2003;Liberi et al 2005). In fission yeast, Rqh1 also interacts with the Top3 ortholog (Ahmad and Stewart 2005).…”

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The Fission Yeast BLM Homolog Rqh1 Promotes Meiotic Recombination

2008

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RecQ helicases are found in organisms as diverse as bacteria, fungi, and mammals. These proteins promote genome stability, and mutations affecting human RecQ proteins underlie premature aging and cancer predisposition syndromes, including Bloom syndrome, caused by mutations affecting the BLM protein. In this study we show that mutants lacking the Rqh1 protein of the fission yeast Schizosaccharomyces pombe, a RecQ and BLM homolog, have substantially reduced meiotic recombination, both gene conversions and crossovers. The relative proportion of gene conversions having associated crossovers is unchanged from that in wild type. In rqh1 mutants, meiotic DNA double-strand breaks are formed and disappear with wild-type frequency and kinetics, and spore viability is only moderately reduced. Genetic analyses and the wild-type frequency of both intersister and interhomolog joint molecules argue against these phenotypes being explained by an increase in intersister recombination at the expense of interhomolog recombination. We suggest that Rqh1 extends hybrid DNA and biases the recombination outcome toward crossing over. Our results contrast dramatically with those from the budding yeast ortholog, Sgs1, which has a meiotic antirecombination function that suppresses recombination events involving more than two DNA duplexes. These observations underscore the multiple recombination functions of RecQ homologs and emphasize that even conserved proteins can be adapted to play different roles in different organisms.

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“…Because both SGS1 and rqh1 ϩ belong to the same family of proteins, the RecQ DNA helicases, this intriguing genetic interaction has led to the suggestion that type IA topoisomerases may be functionally associated with RecQ helicases. Indeed, both Sgs1 and Rqh1 physically interact with Top3 in their respective organisms (Gangloff et al, 1994;Bennett et al, 2000;Fricke et al, 2001;Onodera et al, 2002;Laursen et al, 2003;Ahmad and Stewart, 2005;Ui et al, 2005), and a close association between a RecQ helicase and type IA topoisomerase has now been demonstrated in a number of other organisms (Harmon et al, 1999;Wu et al, 2000;Kim et al, 2002).RecQ helicases are evolutionarily conserved 335Ј DNA helicase enzymes that are important for the maintenance of genomic stability in all organisms (Hickson, 2003). Of particular interest, defects in three (of the five so far identified) human RecQ helicases cause Bloom's syndrome (BLM), RothmundThomson syndrome (RECQL4), and Werner's syndrome (WRN) (Ellis et al, 1995; Yu et al, 1996;Kitao et al, 1999).…”

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Top3 Processes Recombination Intermediates and Modulates Checkpoint Activity after DNA Damage

Mankouri

Hickson

2006

MBoC

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Mutation of TOP3 in Saccharomyces cerevisiae causes poor growth, hyperrecombination, and a failure to fully activate DNA damage checkpoints in S phase. Here, we report that overexpression of a dominant-negative allele of TOP3, TOP3 Y356F , which lacks the catalytic (decatenation) activity of Top3, causes impaired S-phase progression and the persistence of abnormal DNA structures (X-shaped DNA molecules) after exposure to methylmethanesulfonate. The impaired S-phase progression is due to a persistent checkpoint-mediated cell cycle delay and can be overridden by addition of caffeine. Hence, the catalytic activity of Top3 is not required for DNA damage checkpoint activation, but it is required for normal S-phase progression after DNA damage. We also present evidence that the checkpoint-mediated cell cycle delay and persistence of X-shaped DNA molecules resulting from overexpression of TOP3 Y356F are downstream of Rad51 function. We propose that Top3 functions in S phase to both process homologous recombination intermediates and modulate checkpoint activity. INTRODUCTIONTopoisomerases are highly conserved proteins that catalyze topological rearrangements in the structure of DNA and are required for many aspects of DNA metabolism. Of the three topoisomerases in yeast, the function(s) of the sole type IA topoisomerase, Top3, remains most poorly understood. However, it is likely that Top3 fulfills important roles in vivo, because deletion of TOP3 in Saccharomyces cerevisiae causes hyperrecombination, sensitivity to genotoxic agents, meiotic defects, and poor growth due to accumulation of cells with a late S/G 2 content of DNA (Wallis et al., 1989;Gangloff et al., 1994Gangloff et al., , 1999Chakraverty et al., 2001). Similarly, deletion of top3 ϩ in Schizosaccharomyces pombe causes lethality due to chromosome missegregation and accumulation of DNA double-strand breaks (Goodwin et al., 1999;Maftahi et al., 1999;Oh et al., 2002;Win et al., 2004). Whereas lower eukaryotes generally contain only one type IA topoisomerase, human cells, like most vertebrates, possess at least two Top3 homologues, hTOPIII␣ and hTOPIII␤ (Hanai et al., 1996;Ng et al., 1999). In mice, mutation of TOP3␣ causes embryonic lethality (Li and Wang, 1998), whereas mutation of TOP3␤ causes a shortened life span (Kwan et al., 2003). Interestingly, in S. cerevisiae and S. pombe, deletion of SGS1 or rqh1 ϩ can largely suppress the phenotypes caused by deletion of TOP3 or top3 ϩ , respectively (Gangloff et al., 1994;Goodwin et al., 1999;Maftahi et al., 1999;Chakraverty et al., 2001). Because both SGS1 and rqh1 ϩ belong to the same family of proteins, the RecQ DNA helicases, this intriguing genetic interaction has led to the suggestion that type IA topoisomerases may be functionally associated with RecQ helicases. Indeed, both Sgs1 and Rqh1 physically interact with Top3 in their respective organisms (Gangloff et al., 1994;Bennett et al., 2000;Fricke et al., 2001;Onodera et al., 2002;Laursen et al., 2003;Ahmad and Stewart, 2005;Ui et al., 2005), and a close as...

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The N-terminal region of the Schizosaccharomyces pombe RecQ helicase, Rqh1p, physically interacts with Topoisomerase III and is required for Rqh1p function

Cited by 28 publications

References 50 publications

Fission Yeast RecQ Helicase Rqh1 Is Required for the Maintenance of Circular Chromosomes

Fission Yeast RecQ Helicase Rqh1 Is Required for the Maintenance of Circular Chromosomes

The Fission Yeast BLM Homolog Rqh1 Promotes Meiotic Recombination

Top3 Processes Recombination Intermediates and Modulates Checkpoint Activity after DNA Damage

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