A systems biology analysis of protein–protein interactions between yeast superoxide dismutases and DNA repair pathways

The human body is a complex structure of cells, which are exposed to many types of stress. Cells must utilize various mechanisms to protect their DNA from damage caused by metabolic and external sources to maintain genomic integrity and homeostasis and to prevent the development of cancer. DNA damage inevitably occurs regardless of physiological or abnormal conditions. In response to DNA damage, signaling pathways are activated to repair the damaged DNA or to induce cell apoptosis. During the process, posttranslational modifications (PTMs) can be used to modulate enzymatic activities and regulate protein stability, protein localization, and protein-protein interactions. Thus, PTMs in DNA repair should be studied. In this review, we will focus on the current understanding of the phosphorylation, poly(ADP-ribosyl)ation, ubiquitination, SUMOylation, acetylation, and methylation of six typical PTMs and summarize PTMs of the key proteins in DNA repair, providing important insight into the role of PTMs in the maintenance of genome stability and contributing to reveal new and selective therapeutic approaches to target cancers.

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Parasites, proteomes and systems: has Descartes’ clock run out of time?

Parasitology ◽

10.1017/s0031182012000716 ◽

2012 ◽

Vol 139 (9) ◽

pp. 1103-1118 ◽

Cited By ~ 18

Author(s):

J. M. WASTLING ◽

S. D. ARMSTRONG ◽

R. KRISHNA ◽

D. XIA

Keyword(s):

Systems Biology ◽

Protein Interactions ◽

Biological Data ◽

Protein Protein Interactions ◽

Proteomics Data ◽

Data Types ◽

Quality Of Data ◽

Post Translational Modifications ◽

Systems Modelling ◽

New Generation

SUMMARYSystems biology aims to integrate multiple biological data types such as genomics, transcriptomics and proteomics across different levels of structure and scale; it represents an emerging paradigm in the scientific process which challenges the reductionism that has dominated biomedical research for hundreds of years. Systems biology will nevertheless only be successful if the technologies on which it is based are able to deliver the required type and quality of data. In this review we discuss how well positioned is proteomics to deliver the data necessary to support meaningful systems modelling in parasite biology. We summarise the current state of identification proteomics in parasites, but argue that a new generation of quantitative proteomics data is now needed to underpin effective systems modelling. We discuss the challenges faced to acquire more complete knowledge of protein post-translational modifications, protein turnover and protein-protein interactions in parasites. Finally we highlight the central role of proteome-informatics in ensuring that proteomics data is readily accessible to the user-community and can be translated and integrated with other relevant data types.

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Probing the Unknowns in Cytokinin-Mediated Immune Defense in Arabidopsis with Systems Biology Approaches

Bioinformatics and Biology Insights ◽

10.4137/bbi.s13462 ◽

2014 ◽

Vol 8 ◽

pp. BBI.S13462 ◽

Cited By ~ 10

Author(s):

Muhammad Naseem ◽

Meik Kunz ◽

Thomas Dandekar

Keyword(s):

Systems Biology ◽

Immune Responses ◽

Protein Interactions ◽

Immune Defense ◽

Immune Functions ◽

Protein Protein Interactions ◽

Cytokinin Signaling ◽

Host Immune Responses ◽

Arabidopsis Protein ◽

Underlying Mechanisms

Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein—protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants.

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180 Integrating structural and systems biology: structure-based prediction of protein–protein interactions on a genome-wide scale

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2013.786422 ◽

2013 ◽

Vol 31 (sup1) ◽

pp. 116-116

Author(s):

Qiangfeng Cliff Zhang ◽

Donald Petrey ◽

Barry Honig

Keyword(s):

Systems Biology ◽

Protein Interactions ◽

Protein Protein Interactions ◽

Genome Wide ◽

A Genome ◽

Wide Scale

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Identification of Novel Inhibitory Peptides of Protein-Protein Interactions Involved in DNA Repair as Potential Drugs in Breast Cancer Treatment

10.21236/ada398548 ◽

2001 ◽

Cited By ~ 1

Author(s):

William T. Beck

Keyword(s):

Breast Cancer ◽

Dna Repair ◽

Cancer Treatment ◽

Protein Interactions ◽

Breast Cancer Treatment ◽

Protein Protein Interactions ◽

Inhibitory Peptides

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Systems Perspective of Morbillivirus Replication

Journal of Molecular Microbiology and Biotechnology ◽

10.1159/000448842 ◽

2016 ◽

Vol 26 (6) ◽

pp. 389-400 ◽

Cited By ~ 2

Author(s):

Naveen Kumar ◽

Sanjay Barua ◽

Riyesh Thachamvally ◽

Bhupendra Nath Tripathi

Keyword(s):

Immune Response ◽

Disease Resistance ◽

Systems Biology ◽

Protein Interactions ◽

Protein Protein Interactions ◽

Host Proteins ◽

Systems Perspective ◽

Host Pathogen Interaction ◽

Comprehensive Information

Systems biology refers to system-wide changes in biological components such as RNA/DNA (genomics), protein (proteomics) and lipids (lipidomics). In this review, we provide comprehensive information about morbillivirus replication. Besides discussing the role of individual viral/host proteins in virus replication, we also discuss how systems-level analyses could improve our understanding of morbillivirus replication, host-pathogen interaction, immune response and disease resistance. Finally, we discuss how viroinformatics is likely to provide important insights for understanding genome-genome, genome-protein and protein-protein interactions.

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Modulation of the Apurinic/Apyrimidinic Endonuclease Activity of Human APE1 and of Its Natural Polymorphic Variants by Base Excision Repair Proteins

International Journal of Molecular Sciences ◽

10.3390/ijms21197147 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7147

Author(s):

Olga A. Kladova ◽

Irina V. Alekseeva ◽

Murat Saparbaev ◽

Olga S. Fedorova ◽

Nikita A. Kuznetsov

Keyword(s):

Dna Repair ◽

Binding Site ◽

Base Excision Repair ◽

Protein Interactions ◽

Excision Repair ◽

Dna Glycosylases ◽

Protein Protein Interactions ◽

Dna Binding Site ◽

Polymorphic Variants ◽

Base Excision

Human apurinic/apyrimidinic endonuclease 1 (APE1) is known to be a critical player of the base excision repair (BER) pathway. In general, BER involves consecutive actions of DNA glycosylases, AP endonucleases, DNA polymerases, and DNA ligases. It is known that these proteins interact with APE1 either at upstream or downstream steps of BER. Therefore, we may propose that even a minor disturbance of protein–protein interactions on the DNA template reduces coordination and repair efficiency. Here, the ability of various human DNA repair enzymes (such as DNA glycosylases OGG1, UNG2, and AAG; DNA polymerase Polβ; or accessory proteins XRCC1 and PCNA) to influence the activity of wild-type (WT) APE1 and its seven natural polymorphic variants (R221C, N222H, R237A, G241R, M270T, R274Q, and P311S) was tested. Förster resonance energy transfer–based kinetic analysis of abasic site cleavage in a model DNA substrate was conducted to detect the effects of interacting proteins on the activity of WT APE1 and its single-nucleotide polymorphism (SNP) variants. The results revealed that WT APE1 activity was stimulated by almost all tested DNA repair proteins. For the SNP variants, the matters were more complicated. Analysis of two SNP variants, R237A and G241R, suggested that a positive charge in this area of the APE1 surface impairs the protein–protein interactions. In contrast, variant R221C (where the affected residue is located near the DNA-binding site) showed permanently lower activation relative to WT APE1, whereas neighboring SNP N222H did not cause a noticeable difference as compared to WT APE1. Buried substitution P311S had an inconsistent effect, whereas each substitution at the DNA-binding site, M270T and R274Q, resulted in the lowest stimulation by BER proteins. Protein–protein molecular docking was performed between repair proteins to identify amino acid residues involved in their interactions. The data uncovered differences in the effects of BER proteins on APE1, indicating an important role of protein–protein interactions in the coordination of the repair pathway.

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