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Author

Georgios I. Karras

Other affiliations: Max Planck Society
Bio: Georgios I. Karras is an academic researcher from Massachusetts Institute of Technology. The author has contributed to research in topics: DNA repair & Eukaryotic DNA replication. The author has an hindex of 10, co-authored 10 publications receiving 2018 citations. Previous affiliations of Georgios I. Karras include Max Planck Society.

Papers
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Journal ArticleDOI
31 Aug 2012-Cell
TL;DR: In this paper, the authors systematically and quantitatively surveyed most human kinases, transcription factors, and E3 ligases for interaction with HSP90 and its cochaperone CDC37.

732 citations

Journal ArticleDOI
TL;DR: In this article, the authors provide biochemical and structural evidence that macro domains are high affinity binding modules for ADP-ribose nucleotide nucleotides and reveal a conserved ligand binding pocket among the macro domain fold.
Abstract: The ADP-ribosylation of proteins is an important post-translational modification that occurs in a variety of biological processes, including DNA repair, transcription, chromatin biology and long-term memory formation. Yet no protein modules are known that specifically recognize the ADP-ribose nucleotide. We provide biochemical and structural evidence that macro domains are high-affinity ADP-ribose binding modules. Our structural analysis reveals a conserved ligand binding pocket among the macro domain fold. Consistently, distinct human macro domains retain their ability to bind ADP-ribose. In addition, some macro domain proteins also recognize poly-ADP-ribose as a ligand. Our data suggest an important role for proteins containing macro domains in the biology of ADP-ribose.

476 citations

Journal ArticleDOI
23 Apr 2015-Cell
TL;DR: This work functionally profile several thousand missense mutations across a spectrum of Mendelian disorders using various interaction assays, suggesting that disease-associated alleles that perturb distinct protein activities rather than grossly affecting folding and stability are relatively widespread.

453 citations

Journal ArticleDOI
16 Apr 2010-Cell
TL;DR: These findings indicate that both branches of the DNA damage tolerance pathway operate effectively after chromosomal replication, outside S phase, and propose that the RAD6 pathway acts on single-stranded gaps left behind newly restarted replication forks.

284 citations

Journal ArticleDOI
23 Feb 2017-Cell
TL;DR: A compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding and provides one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases.

107 citations


Cited by
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Journal ArticleDOI
TL;DR: This review will focus on how the DDR controls DNA repair and the phenotypic consequences of defects in these critical regulatory functions in mammals.

3,678 citations

Journal ArticleDOI
TL;DR: The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD+, is a unique post-translational modification that regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated.
Abstract: The addition to proteins of the negatively charged polymer of ADP-ribose (PAR), which is synthesized by PAR polymerases (PARPs) from NAD(+), is a unique post-translational modification. It regulates not only cell survival and cell-death programmes, but also an increasing number of other biological functions with which novel members of the PARP family have been associated. These functions include transcriptional regulation, telomere cohesion and mitotic spindle formation during cell division, intracellular trafficking and energy metabolism.

1,820 citations

Journal Article
TL;DR: Why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease are detailed.
Abstract: Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

1,323 citations

Journal ArticleDOI
TL;DR: How the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells is outlined.
Abstract: Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress. Here, we outline how the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells. Considerable advances have also been made in understanding the underlying molecular mechanisms for these events, with post-translational modifications of DDR factors being shown to play prominent roles in controlling the formation of foci in response to DNA-damaging agents. We review these regulatory mechanisms and discuss their biological significance to the DDR.

1,051 citations

Journal ArticleDOI
TL;DR: A new dedicated aspect of BioGRID annotates genome-wide CRISPR/Cas9-based screens that report gene–phenotype and gene–gene relationships, and captures chemical interaction data, including chemical–protein interactions for human drug targets drawn from the DrugBank database and manually curated bioactive compounds reported in the literature.
Abstract: The Biological General Repository for Interaction Datasets (BioGRID: https://thebiogrid.org) is an open access database dedicated to the curation and archival storage of protein, genetic and chemical interactions for all major model organism species and humans. As of September 2018 (build 3.4.164), BioGRID contains records for 1 598 688 biological interactions manually annotated from 55 809 publications for 71 species, as classified by an updated set of controlled vocabularies for experimental detection methods. BioGRID also houses records for >700 000 post-translational modification sites. BioGRID now captures chemical interaction data, including chemical-protein interactions for human drug targets drawn from the DrugBank database and manually curated bioactive compounds reported in the literature. A new dedicated aspect of BioGRID annotates genome-wide CRISPR/Cas9-based screens that report gene-phenotype and gene-gene relationships. An extension of the BioGRID resource called the Open Repository for CRISPR Screens (ORCS) database (https://orcs.thebiogrid.org) currently contains over 500 genome-wide screens carried out in human or mouse cell lines. All data in BioGRID is made freely available without restriction, is directly downloadable in standard formats and can be readily incorporated into existing applications via our web service platforms. BioGRID data are also freely distributed through partner model organism databases and meta-databases.

1,046 citations