Institute for Chemical Immunology

Leiden, Netherlands

Institute for Chemical Immunology

Leiden, Netherlands
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van Elsland D.M.,Leiden University | van Elsland D.M.,Institute for Chemical Immunology | Bos E.,Leiden University | Overkleeft H.S.,Leiden University | And 4 more authors.
Journal of Chemical Biology | Year: 2015

With correlative light and electron microscopy (CLEM), the ultrastructural cellular location of a biomolecule of interest can be determined using a combination of light microscopy (LM) and electron microscopy (EM). In many cases, the application of CLEM requires the use of markers that need to be attached to a biomolecule of interest to allow its identification and localization. Here, we review the potential of bioorthogonal chemistry to introduce such markers for CLEM. © 2015, The Author(s).


Pang B.,Netherlands Cancer Institute | De Jong J.,Netherlands Cancer Institute | Qiao X.,Netherlands Cancer Institute | Wessels L.F.A.,Netherlands Cancer Institute | And 2 more authors.
Nature Chemical Biology | Year: 2015

Many anticancer drugs induce DNA breaks to eliminate tumor cells. The anthracycline topoisomerase II inhibitors additionally cause histone eviction. Here, we performed genome-wide high-resolution mapping of chemotherapeutic effects of various topoisomerase I and II (TopoI and II) inhibitors and integrated this mapping with established maps of genomic or epigenomic features to show their activities in different genomic regions. The TopoI inhibitor topotecan and the TopoII inhibitor etoposide are similar in inducing DNA damage at transcriptionally active genomic regions. The anthracycline daunorubicin induces DNA breaks and evicts histones from active chromatin, thus quenching local DNA damage responses. Another anthracycline, aclarubicin, has a different genomic specificity and evicts histones from H3K27me3-marked heterochromatin, with consequences for diffuse large B-cell lymphoma cells with elevated levels of H3K27me3. Modifying anthracycline structures may yield compounds with selectivity for different genomic regions and activity for different tumor types. © 2015 Nature America, Inc. All rights reserved.

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