Article

Fanconi-like crosslink repair in yeast

Genome integrity 10/2012; 3(1):7. DOI: 10.1186/2041-9414-3-7
Source: PubMed

ABSTRACT Interstrand crosslinks covalently link complementary DNA strands, block replication and transcription, and can trigger cell death. In eukaryotic systems several pathways, including the Fanconi Anemia pathway, are involved in repairing interstrand crosslinks, but their precise mechanisms remain enigmatic. The lack of functional homologs in simpler model organisms has significantly hampered progress in this field. Two recent studies have finally identified a Fanconi-like interstrand crosslink repair pathway in yeast. Future studies in this simplistic model organism promise to greatly improve our basic understanding of complex interstrand crosslink repair pathways like the Fanconi pathway.

1 Follower
 · 
137 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pso2 protein, a member of the highly conserved metallo-β-lactamase (MBL) super family of nucleases, plays a central role in interstrand crosslink repair (ICL) in yeast. Pso2 protein is the founder member of a distinct group within the MBL superfamily, called β-CASP family. Three mammalian orthologs of this protein that act on DNA were identified: SNM1A, SNM1B/Apollo and SNM1C/Artemis. Yeast Pso2 and all three mammalian orthologs proteins have been shown to possess nuclease activity. Besides Pso2, ICL repair involves proteins of several DNA repair pathways. Over the last years, new homologs for human proteins have been identified in yeast. In this review, we will focus on studies clarifying the function of Pso2 protein during ICL repair in yeast, emphasizing the contribution of Brazilian research groups in this topic. New sub-pathways in the mechanisms of ICL repair, such as recently identified conserved Fanconi Anemia pathway in yeast as well as a contribution of non-homologous end joining are discussed.
    Fungal Genetics and Biology 09/2013; 60. DOI:10.1016/j.fgb.2013.09.003 · 3.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3'-5' helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres in vivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to a role in ICL repair and/or suppression of de novo telomere addition.
    Cell Reports 01/2014; 6(2). DOI:10.1016/j.celrep.2013.12.037 · 7.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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 coordi-nate DNA replication with chromosome segregation in this organism. A number of recent and ongoing studies have dem-onstrated that Tus-Ter can be used as a heterologous tool to generate site-specific 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 regu-latable RF blocking system that can be utilized for disrupting DNA replication in a diverse range of host cells.
    Cell cycle (Georgetown, Tex.) 10/2014; 13(19):2994. DOI:10.4161/15384101.2014.958912 · 5.01 Impact Factor

Preview

Download
1 Download
Available from