Movement and Specificity in a Modular DNA Binding Protein

Liptak, Cary; Loria, J. Patrick

doi:10.1016/j.str.2015.05.004

Cited by 2 publications

(2 citation statements)

References 5 publications

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“…These include proteins of the HR pathway, such as components of the MRN complex (mre11 and Rad50) and the RPA complex (Replication Protein A complex, consisting of Rpa-70, RPA2 and RPA3). RPA is the major ssDNA-binding protein complex during DNA resection (36). We also found proteins of the non-homologous end joining (NHEJ) pathway (Ku70/Irbp and Ku80).…”

Section: Resultsmentioning

confidence: 99%

A Drosophila cell-free system that senses DNA breaks and triggers phosphorylation signalling

Harpprecht

Baldi

Schauer

et al. 2019

Nucleic Acids Research

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Preblastoderm Drosophila embryo development is characterized by fast cycles of nuclear divisions. Extracts from these embryos can be used to reconstitute complex chromatin with high efficiency. We now discovered that this chromatin assembly system contains activities that recognize unprotected DNA ends and signal DNA damage through phosphorylation. DNA ends are initially bound by Ku and MRN complexes. Within minutes, the phosphorylation of H2A.V (homologous to γH2A.X) initiates from DNA breaks and spreads over tens of thousands DNA base pairs. The γH2A.V phosphorylation remains tightly associated with the damaged DNA and does not spread to undamaged DNA in the same reaction. This first observation of long-range γH2A.X spreading along damaged chromatin in an in vitro system provides a unique opportunity for mechanistic dissection. Upon further incubation, DNA ends are rendered single-stranded and bound by the RPA complex. Phosphoproteome analyses reveal damage-dependent phosphorylation of numerous DNA-end-associated proteins including Ku70, RPA2, CHRAC16, the exonuclease Rrp1 and the telomer capping complex. Phosphorylation of spindle assembly checkpoint components and of microtubule-associated proteins required for centrosome integrity suggests this cell-free system recapitulates processes involved in the regulated elimination of fatally damaged syncytial nuclei.

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Section: Resultsmentioning

confidence: 99%

A Drosophila cell-free system that senses DNA breaks and triggers phosphorylation signalling

Harpprecht

Baldi

Schauer

et al. 2019

Nucleic Acids Research

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“…Classification of DNA-binding domains; adopted from Gonzales et al [86] and modified according to Wingender [93]. One of the defining characteristics of DBDs is their modular nature, allowing them to be isolated from the rest of the transcription factor without loss of function and therefore allowing the study of multiple effects [94]. This modularity is advantageous for structural studies, facilitating techniques like crystallization or nuclear magnetic resonance (NMR) spectroscopy.…”

Section: Classification Characteristics and Functionmentioning

confidence: 99%

Role of Natural Binding Proteins in Therapy and Diagnostics

Eigenfeld,

Lupp,

Schwaminger

2024

Life

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This review systematically investigates the critical role of natural binding proteins (NBPs), encompassing DNA-, RNA-, carbohydrate-, fatty acid-, and chitin-binding proteins, in the realms of oncology and diagnostics. In an era where cancer continues to pose significant challenges to healthcare systems worldwide, the innovative exploration of NBPs offers a promising frontier for advancing both the diagnostic accuracy and therapeutic efficacy of cancer management strategies. This manuscript provides an in-depth examination of the unique mechanisms by which NBPs interact with specific molecular targets, highlighting their potential to revolutionize cancer diagnostics and therapy. Furthermore, it discusses the burgeoning research on aptamers, demonstrating their utility as ‘nucleic acid antibodies’ for targeted therapy and precision diagnostics. Despite the promising applications of NBPs and aptamers in enhancing early cancer detection and developing personalized treatment protocols, this review identifies a critical knowledge gap: the need for comprehensive studies to understand the diverse functionalities and therapeutic potentials of NBPs across different cancer types and diagnostic scenarios. By bridging this gap, this manuscript underscores the importance of NBPs and aptamers in paving the way for next-generation diagnostics and targeted cancer treatments.

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Movement and Specificity in a Modular DNA Binding Protein

Cited by 2 publications

References 5 publications

A Drosophila cell-free system that senses DNA breaks and triggers phosphorylation signalling

A Drosophila cell-free system that senses DNA breaks and triggers phosphorylation signalling

Role of Natural Binding Proteins in Therapy and Diagnostics

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