Novel endonuclease in Archaea cleaving DNA with various branched structure.

Komori, Keishi; Fujikane, Ryosuke; Shinagawa, Hideo; Ishino, Yuji

doi:10.1266/ggs.77.227

Cited by 86 publications

(81 citation statements)

References 59 publications

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“…We propose that Mph1 stimulates the endonuclease Mms4/Mus81, since we found an epistatic relationship of mms4 and mus81 to mph1 in terms of sensitivity to camptothecin. Further circumstantial support comes from the findings that in the Mph1 archaeal homologue, Hef, the N-terminal helicase stimulates the endonucleolytic activity of the C-terminal domain (Komori et al, 2002). Proper resolution via Mms4/Mus81-Mph1 would allow replication restart ( Figure 6D).…”

Section: Mph1 Is Likely To Have a Role In Recombinational Dna Repair mentioning

confidence: 98%

“…biochemical data suggesting that the Mph1-like and Mus81-like domains of archaeal Hef protein cooperatively resolve stalled replication forks (Komori et al, 2002), prompted us to investigate the genetic interaction between mph1 and mms4-mus81 mutations for sensitivity to DNA damaging agents. As previously reported (Bastin-Shanower et al, 2003), we observed mms4 and mus81 single mutants to be sensitive to MMS, 4-NQO and camptothecin ( Figure 3C, D).…”

Section: Genetic Interactions Of Rad54 and Mms4-mus81 With Mph1mentioning

confidence: 99%

“…A recent work by Prakash et al (2009) described the ability of purified Mph1 to bind D-loop structures and to unwind these DNA structures, although it is probably not its only function since it would not explain the mph1 mutator phenotype (Scheller et al, 2000). S. cerevisiae Mph1 shows sequence similarity to human FANCM and the archaeabacterial Hef (Komori et al, 2002;Meetei et al, 2005). FANCM belongs to the Fanconi Anemia (FA) pathway (Meetei et al, 2005) regulating a cellular response to genotoxic stresses (Kennedy and D'Andrea, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…It has a conserved helicaseATPase domain showing ATP-dependent DNA translocase activity and an endonuclease domain homologous to S. cerevisiae Mus81 endonuclease (Meetei et al, 2005). The archaeabacterial Hef protein consists of two domains; the helicase domain similar to Mph1 and the C-terminal domain with some sequence similarity to Mus81 (Komori et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Panico

Ede

Schildmann

et al. 2009

Yeast

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In yeast as in human, DNA helicases play critical roles in assisting replication fork progression. The Saccharomyces cerevisiae MPH1 gene, homologue of human FANCM, has been involved in homologous recombination and DNA repair. We describe a synthetic growth defect of an mph1 deletion if combined with an srs2 deletion that can result -depending on the genetic background -in synthetic lethality. The lethality is suppressed by mutations in homologous recombination (rad51, rad52, rad55, rad57 ) and in the DNA damage checkpoint (rad9, rad24, rad17 ). Importantly, rad54 and mph1, epistatic for damage sensitivity, are subadditive for spontaneous mutator phenotype. Therefore, Mph1 could be placed at the Rad51-mediated strand invasion process, with a function distinct from Rad54. Moreover, siz1 mutation is viable with mph1 and additive for DNA damage sensitivity. mph1 srs2 double mutants, isolated in a background where they are viable, are synergistically sensitive to DNA damage. Moderate overexpression of SGS1 partially suppresses this sensitivity. Finally, we observe an epistatic relationship in terms of sensitivity to camptothecin of mms4 or mus81 to mph1. Overall, our results support a role of Mph1 in assisting replication progression. We propose two models for the resumption of DNA synthesis under replicative stress where Mph1 is placed at the sister chromatid interaction step.

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Section: Mph1 Is Likely To Have a Role In Recombinational Dna Repair mentioning

confidence: 98%

Section: Genetic Interactions Of Rad54 and Mms4-mus81 With Mph1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Panico

Ede

Schildmann

et al. 2009

Yeast

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“…Hef was originally described in archaebacteria as a protein that could process blocked DNA replication forks into double-strand DNA breaks (Komori et al 2002). Meetei et al (2005) identified the human ortholog of Hef as a 250-kDa component of complex 1 using coimmunoprecipitation experiments.…”

Section: Fancm Is the Mammalian Ortholog Of Hefmentioning

confidence: 99%

The Fanconi Anemia/BRCA pathway: new faces in the crowd

Kennedy¹,

D’Andrea²

2005

Genes Dev.

362

345

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Over the past few years, study of the rare inherited chromosome instability disorder, Fanconi Anemia (FA), has uncovered a novel DNA damage response pathway. Through the cooperation of multiple proteins, this pathway regulates a complicated cellular response to DNA cross-linking agents and other genotoxic stresses. In this article we review recent data identifying new components of the FA pathway that implicate it in several aspects of the DNA damage response, including the direct processing of DNA, translesion synthesis, homologous recombination, and cell cycle regulation. We also discuss new findings that explain how the FA pathway is regulated through the processes of ubiquitination and deubiquitination. We then consider the clinical implications of our current understanding of the FA pathway, particularly in the development and treatment of malignancy in heterozygous carriers of FA mutations or in patients with sporadic cancers. We consider how recent studies of p53-mediated apoptosis and loss of p53 function in models of FA may help explain the clinical features of the disease and finally present a hypothesis to account for the specificity of the FA pathway in the response to DNA cross-links.

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Early Evolution of DNA Repair Mechanisms

DiRuggiero

Robb

2004

The Genetic Code and the Origin of Life

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DNA repair is critical for the maintenance of genome integrity and replication fidelity in all cells, and therefore was arguably of major importance in the Last Universal Cellular Ancestor (LUCA) as well. Archaea, and hyperthermophiles in particular, are well suited for studying early DNA repair mechanisms from two perspeaives. First, these prokaryotes embody a mix of bacterial and eukaryal molecular features. Second, DNA in many archaea is subject to ongoing damage during normal growth under extreme conditions such as high temperature or low pH. Third, recent work suggests that the mutation rates of model hyperthermophiles are quite close to norms for bacteria, indicating that their replication/repair processes are operating with high fidelity at elevated temperatures. The Archaea also have minimal sets of genes involved in all of the major cellular information transfer processes, compared with Eukarya, which have highly paralogous and redundant sets of genes for DNA replication, repair and recombination.Repair activities have been demonstrated for several hyperthermophiles including our studies with Pyrococcus furiosus, an archaeon growing optimally at 100°C. In addition, using comparative genomic analysis and the genome sequence of several hyperthermophilic archaea, homologs of conserved eukaryotic and bacterial DNA repair proteins have been identified. Although close to 100 microbial genome sequences have been analyzed, including 16 from the Archaea, so far many highly conserved repair genes are missing in some or in all of the archaeal genomes. This may be the result of low sequence conservation across the three domains of life, preventing identification using sequence similarity searches. It is possible, and proven in some instances, that Archaea have novel versions of repair proteins.Here we argue that the commonality of mechanisms and protein sequences, shared between prokaryotes and eukaryotes for several modes of DNA repair, reflects diversification from a minimal set of genes. However, for several pathways, the close similarity between components of eukaryal and archaeal repair pathways suggests that those specific processes likely evolved independendy in the bacterial and archaeal/eukaryal lineages.

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Novel endonuclease in Archaea cleaving DNA with various branched structure.

Cited by 86 publications

References 59 publications

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

Genetic evidence for a role of Saccharomyces cerevisiae Mph1 in recombinational DNA repair under replicative stress

The Fanconi Anemia/BRCA pathway: new faces in the crowd

Early Evolution of DNA Repair Mechanisms

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