Track topics on Twitter Track topics that are important to you
DNA double-strand breaks (DSBs) induced by genotoxic agents can cause cell death or contribute to chromosomal instability, a major driving force of cancer. By contrast, Spo11-dependent DSBs formed during meiosis are aimed at generating genetic diversity. In eukaryotes, CtIP and the Mre11 nuclease complex are essential for accurate processing and repair of both unscheduled and programmed DSBs by homologous recombination (HR). Here, we applied bioinformatics and genetic analysis to identify Paramecium tetraurelia CtIP (PtCtIP), the smallest known Sae2/Ctp1/CtIP ortholog, as a key factor for the completion of meiosis and the recovery of viable sexual progeny. Using in vitro assays, we find that purified recombinant PtCtIP preferentially binds to double-stranded DNA substrates but does not contain intrinsic nuclease activity. Moreover, mutation of the evolutionarily conserved C-terminal 'RHR' motif abrogates DNA binding of PtCtIP but not its ability to functionally interact with Mre11. Translating our findings into mammalian cells, we provide evidence that disruption of the 'RHR' motif abrogates accumulation of human CtIP at sites of DSBs. Consequently, cells expressing the DNA binding mutant CtIP are defective in DSB resection and HR. Collectively, our work highlights minimal structural requirements for CtIP protein family members to facilitate the processing of DSBs, thereby maintaining genome stability as well as enabling sexual reproduction.
This article was published in the following journal.
Name: DNA repair
Chain-terminating nucleoside analogs (CTNAs), which cannot be extended by DNA polymerases, are widely used as antivirals or anti-cancer agents, and can induce cell death. Processing of blocked DNA end...
Ciliates are the largest group of ubiquitous aquatic bacterivorous protists, and many species are easily cultivated. However, only few studies reported prokaryotic communities naturally associated wit...
Miniature inverted-repeat transposable elements (MITEs) are short, non-autonomous class II transposable elements present in a high number of conserved copies in eukaryote genomes. An accurate identifi...
The evolution of mitochondrial genomes and their population-genetic environment among unicellular eukaryotes are understudied. Ciliate mitochondrial genomes exhibit a unique combination of characteris...
Miniature insects fly at very low Reynolds number (Re); low Re means large viscous effect. If flapping as larger insects, sufficient vertical force cannot be produced. We measure the wing kinematics f...
This is a 5-year study of patients implanted with the Implantable Miniature Telescope (IMT by Dr. Isaac Lipshitz) under Protocol IMT-002. All patients implanted with the telescope prosthe...
VisionCare's Implantable Miniature Telescope (IMT, intraocular telescope or telescope) is indicated for monocular implantation to improve vision in eyes of patients at least 65 years of ag...
This pilot clinical trial studies radiofrequency technology in locating non-palpable breast lesions in patients undergoing surgery. Placing a miniature radiofrequency tag or microchip in t...
This is a prospective cohort study. All patients presenting for periprosthetic joint infection and requiring debridement only or resection arthroplasty will be eligible. The synovial joint...
The overall aim of this study is to develop an automated spinal landmark identification system to improve patient safety and efficacy of neuraxial procedure needle insertion success. ...
Genetically developed small pigs for use in biomedical research. There are several strains - Yucatan miniature, Sinclair miniature, and Minnesota miniature.
Postsynaptic potentials generated from a release of neurotransmitters from a presynaptic nerve terminal in the absence of an ACTION POTENTIAL. They may be m.e.p.p.s (miniature EXCITATORY POSTSYNAPTIC POTENTIALS) or m.i.p.p.s (miniature INHIBITORY POSTSYNAPTIC POTENTIALS).
A species of ciliated PARAMECIUM possessing two micronuclei.
The most widely distributed species of PARAMECIUM. It is elongated and possesses a bluntly pointed posterior.
A species of ciliate protozoa. It is used in biomedical research.
The World Health Organization (WHO) definition of sexual health; "the state of physical, emotional, mental and social well-being related to sexuality; it is not merely the absence of disease, dysfunction and infirmity. Sexual health requires a posit...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...