DNA damage in mammalian cells leads to activation of the cell cycle regulator Chk2, which triggers downstream degradations of a core clock component, PER (i.e., PER1 in mice). This, in turn, creates unique phase shifts (mostly advances) in the circadian clock. Computational analyses from Hong et al. (doi:10.1371/journal.pcbi.1000384) recapitulate a phase advance (dashed curve) when DNA damage occurs around the peak of PER abundance, but minimum phase shifts around the trough (dots). The model proposes a molecular mechanism behind this phenomenon: differential degradation of PER in the presence of an essential positive feedback loop in the circadian system.
Image Credit: Judit Zámborszky (CoSBi, Microsoft Research-University of Trento Centre for Computational and Systems Biology, Italy).
Messages from ISCB
Getting Started in Computational Mass Spectrometry–Based Proteomics
PLOS Computational Biology: published May 29, 2009 | https://doi.org/10.1371/journal.pcbi.1000366
BioLINK Special Interest Group Session on the Future of Scientific Publishing
PLOS Computational Biology: published May 29, 2009 | https://doi.org/10.1371/journal.pcbi.1000398
Perspective
Hypergraphs and Cellular Networks
PLOS Computational Biology: published May 29, 2009 | https://doi.org/10.1371/journal.pcbi.1000385
Review
What Is Stochastic Resonance? Definitions, Misconceptions, Debates, and Its Relevance to Biology
PLOS Computational Biology: published May 29, 2009 | https://doi.org/10.1371/journal.pcbi.1000348
Research Articles
Fast Statistical Alignment
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A Correspondence Between Solution-State Dynamics of an Individual Protein and the Sequence and Conformational Diversity of its Family
PLOS Computational Biology: published May 29, 2009 | https://doi.org/10.1371/journal.pcbi.1000393
Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks
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Brain Anatomical Network and Intelligence
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SHRiMP: Accurate Mapping of Short Color-space Reads
PLOS Computational Biology: published May 22, 2009 | https://doi.org/10.1371/journal.pcbi.1000386
Computational Models of the Notch Network Elucidate Mechanisms of Context-dependent Signaling
PLOS Computational Biology: published May 22, 2009 | https://doi.org/10.1371/journal.pcbi.1000390
How to Get the Most out of Your Curation Effort
PLOS Computational Biology: published May 22, 2009 | https://doi.org/10.1371/journal.pcbi.1000391
Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors
PLOS Computational Biology: published May 15, 2009 | https://doi.org/10.1371/journal.pcbi.1000387
Molecular Mechanics of the α-Actinin Rod Domain: Bending, Torsional, and Extensional Behavior
PLOS Computational Biology: published May 15, 2009 | https://doi.org/10.1371/journal.pcbi.1000389
Differential Affinity and Catalytic Activity of CheZ in E. coli Chemotaxis
PLOS Computational Biology: published May 8, 2009 | https://doi.org/10.1371/journal.pcbi.1000378
Smoothing of, and Parameter Estimation from, Noisy Biophysical Recordings
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Pairwise Maximum Entropy Models for Studying Large Biological Systems: When They Can Work and When They Can't
PLOS Computational Biology: published May 8, 2009 | https://doi.org/10.1371/journal.pcbi.1000380
A Structure-Based Approach for Detection of Thiol Oxidoreductases and Their Catalytic Redox-Active Cysteine Residues
PLOS Computational Biology: published May 8, 2009 | https://doi.org/10.1371/journal.pcbi.1000383
Minimum Criteria for DNA Damage-Induced Phase Advances in Circadian Rhythms
PLOS Computational Biology: published May 8, 2009 | https://doi.org/10.1371/journal.pcbi.1000384
Representation of Time-Varying Stimuli by a Network Exhibiting Oscillations on a Faster Time Scale
PLOS Computational Biology: published May 1, 2009 | https://doi.org/10.1371/journal.pcbi.1000370
Predictive Feedback Can Account for Biphasic Responses in the Lateral Geniculate Nucleus
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Prediction of Protein Binding Regions in Disordered Proteins
PLOS Computational Biology: published May 1, 2009 | https://doi.org/10.1371/journal.pcbi.1000376
Dating the Age of the SIV Lineages That Gave Rise to HIV-1 and HIV-2
PLOS Computational Biology: published May 1, 2009 | https://doi.org/10.1371/journal.pcbi.1000377
Functional Brain Networks Develop from a “Local to Distributed” Organization
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A Differential Wiring Analysis of Expression Data Correctly Identifies the Gene Containing the Causal Mutation
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