A prototypical Fanconi anemia pathway in lower eukaryotes?

McHugh, Peter J.; Ward, Thomas A.; Chovanec, Miroslav

doi:10.4161/cc.21727

Cited by 29 publications

(38 citation statements)

References 57 publications

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“…With regards to the latter possibility, it is worth noting that mammalian cells have a much more complex Fanconi anemia pathway for dealing with RF stress than that proposed to exist in yeast. 26,27 Although our mutational analyses are consistent with the locking-C6 model 22 for polar RF-stalling at Tus-Ter (Fig. 1), it still remains unclear how such a mechanism could occur when the yeast replisome machinery encounters Tus-Ter.…”

Section: Discussionsupporting

confidence: 82%

Tus-Teras a tool to study site-specific DNA replication perturbation in eukaryotes

2014

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T he high-affinity binding of the Tus protein to specific 21-bp sequences, called Ter, causes site-specific, and polar, DNA replication fork arrest in E coli. The Tus-Ter complex serves to coordinate DNA replication with chromosome segregation in this organism. A number of recent and ongoing studies have demonstrated that Tus-Ter can be used as a heterologous tool to generate sitespecific perturbation of DNA replication when reconstituted in eukaryotes. Here, we review these recent findings and explore the molecular mechanism by which Tus-Ter mediates replication fork (RF) arrest in the budding yeast, S. cerevisiae. We propose that Tus-Ter is a versatile, genetically tractable, and regulatable RF blocking system that can be utilized for disrupting DNA replication in a diverse range of host cells.

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Section: Discussionsupporting

confidence: 82%

Tus-Teras a tool to study site-specific DNA replication perturbation in eukaryotes

2014

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“…Both Fml1 and Mph1 are involved in ICL repair (Daee et al 2012;McHugh et al 2012;Ward et al 2012;Fontebasso et al 2013), but the repair function of Mph1 is only apparent in the absence of an exonuclease capable of degrading the oligonucleotide stemming from ICL unhooking. The fact that S. pombe and S. cerevisiae contain only a few equivalents of FA proteins suggests a major difference in the mechanism of ICL repair in these organisms compared with higher eukaryotes.…”

Section: Roles Of Schizosaccharomyces Pombe Fml1 and Saccharomyces Cementioning

confidence: 99%

Functions and regulation of the multitasking FANCM family of DNA motor proteins

2015

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Members of the conserved FANCM family of DNA motor proteins play key roles in genome maintenance processes. FANCM supports genome duplication and repair under different circumstances and also functions in the ATR-mediated DNA damage checkpoint. Some of these roles are shared among lower eukaryotic family members. Human FANCM has been linked to Fanconi anemia, a syndrome characterized by cancer predisposition, developmental disorder, and bone marrow failure. Recent studies on human FANCM and its orthologs from other organisms have provided insights into their biological functions, regulation, and collaboration with other genome maintenance factors. This review summarizes the progress made, with the goal of providing an integrated view of the functions and regulation of these enzymes in humans and model organisms and how they advance our understanding of genome maintenance processes.

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“…In contrast to humans, where the Fanconi anemia pathway has been well characterized to act on this type of DNA damage, yeast has fewer known factors that are specialized in repairing this type of lesion (38). However, in both yeast and humans, HR plays an important role in the repair of interstrand cross-links.…”

Section: ϫ5mentioning

confidence: 99%

The Budding Yeast Ubiquitin Protease Ubp7 Is a Novel Component Involved in S Phase Progression

Böhm

Szakál²,

Herken

et al. 2016

Journal of Biological Chemistry

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DNA damage must be repaired in an accurate and timely fashion to preserve genome stability. Cellular mechanisms preventing genome instability are crucial to human health because genome instability is considered a hallmark of cancer. Collectively referred to as the DNA damage response, conserved pathways ensure proper DNA damage recognition and repair. The function of numerous DNA damage response components is fine-tuned by posttranslational modifications, including ubiquitination. This not only involves the enzyme cascade responsible for conjugating ubiquitin to substrates but also requires enzymes that mediate directed removal of ubiquitin. Deubiquitinases remove ubiquitin from substrates to prevent degradation or to mediate signaling functions. The Saccharomyces cerevisiae deubiquitinase Ubp7 has been characterized previously as an endocytic factor. However, here we identify Ubp7 as a novel factor affecting S phase progression after hydroxyurea treatment and demonstrate an evolutionary and genetic interaction of Ubp7 with DNA damage repair pathways of homologous recombination and nucleotide excision repair. We find that deletion of UBP7 sensitizes cells to hydroxyurea and cisplatin and demonstrate that factors that stabilize replication forks are critical under these conditions. Furthermore, ubp7⌬ cells exhibit an S phase progression defect upon checkpoint activation by hydroxyurea treatment. ubp7⌬ mutants are epistatic to factors involved in histone maintenance and modification, and we find that a subset of Ubp7 is chromatin-associated. In summary, our results suggest that Ubp7 contributes to S phase progression by affecting the chromatin state at replication forks, and we propose histone H2B ubiquitination as a potential substrate of Ubp7.

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A prototypical Fanconi anemia pathway in lower eukaryotes?

Cited by 29 publications

References 57 publications

Tus-Teras a tool to study site-specific DNA replication perturbation in eukaryotes

Tus-Teras a tool to study site-specific DNA replication perturbation in eukaryotes

Functions and regulation of the multitasking FANCM family of DNA motor proteins

The Budding Yeast Ubiquitin Protease Ubp7 Is a Novel Component Involved in S Phase Progression

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