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Covalent DNA-protein crosslinks (DPC) are toxic DNA lesions that require repair by global-genome and replication-coupled pathways. How cells respond when RNA polymerases stall at DPCs during transcription is unknown. DPC-seq is new method for the genome-wide mapping of covalent DNA-protein adducts.
ORGANISM(S): Homo sapiens 
Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient DNA replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate - a covalent TOP1-DNA adduct known as a TOP1 cleavage complex (TOP1cc) - is stabi...
ORGANISM(S): Homo sapiens (Human) 
2020-03-13 | PXD017239 | Pride
Suppressing Proteasome Mediated Processing of Topoisomerase II DNA-Protein Adducts Preserves Genome Integrity
Protein–DNA interactions are key to the functionality and stability of the genome. Identification and mapping of protein–DNA interaction interfaces and sites is crucial for understanding DNA-dependent processes. Here, we present a workflow that allows mass spectrometric (MS) identification of protei...
ORGANISM(S): Homo sapiens (Human) Xenopus laevis (African clawed frog) 
2020-10-20 | PXD020290 | Pride
DNA-Protein Crosslink sequencing (DPC-seq) in RPE-1 cells treated with formaldehyde
The catalytic cycle of topoisomerase 2 (TOP2) enzymes proceeds via a transient DNA double-strand break (DSB) intermediate termed the TOP2 cleavage complex (TOP2cc), in which the TOP2 protein is covalently bound to DNA. Anti-cancer agents such as etoposide operate by stabilising TOP2ccs, ultimately g...
ORGANISM(S): Homo sapiens (Human) 
2024-01-26 | PXD046611 | Pride
Objectives The antistaphylococcal pyrrolobenzodiazepine dimer ELB-21 forms multiple adducts with duplex DNA through covalent interactions with appropriately spaced guanine residues; it is now known to form interstrand and intrastrand adducts with oligonucleotide sequences of variable length. We dete...
ORGANISM(S): Staphylococcus aureus 
Breakdown products of some glucosinolates M-bM-^@M-^S defense chemicals of Brassicales M-bM-^@M-^S induce detoxifying enzymes and demonstrate preventive activities against chemically induced tumorigenesis in animal models. However, other breakdown products are genotoxic. 1-Methoxy-3-indolylmethyl al...
ORGANISM(S): Mus musculus 
Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment and prevention of breast cancer in women; however, there is evidence that tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has been reported that tamoxifen may cause non-alcoholic fatty liver di...
ORGANISM(S): Mus musculus 
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