Mechanisms of DNA−protein cross-link formation and repair

Wei, Xiaoying; Peng, Ying; Bryan, Cameron; Yang, Kun

doi:10.1016/j.bbapap.2021.140669

Cited by 19 publications

(28 citation statements)

References 94 publications

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“…Our study demonstrated that removal of AP-protein DPCs by E. coli long-patch BER is less efficient than that of an AP-peptide 10mer adduct, which agrees with the emerging model that DPC proteolysis by the proteasome or specific DPC proteases is required for efficient DPC repair ( 56 ). Since 2014, several proteases have been identified in both yeast and human that are dedicated to DPC proteolysis repair ( 56 ). Whether a DPC protease(s) exits in E. coli warrants future investigation.…”

Section: Discussionsupporting

confidence: 89%

In vitro eradication of abasic site-mediated DNA–peptide/protein cross-links by Escherichia coli long-patch base excision repair

Bryan¹,

Wei²,

Wang³

et al. 2022

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 89%

In vitro eradication of abasic site-mediated DNA–peptide/protein cross-links by Escherichia coli long-patch base excision repair

Bryan¹,

Wei²,

Wang³

et al. 2022

Journal of Biological Chemistry

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“…2−4 DPCs also form in biological contexts as intermediates during enzymatic processing of DNA or as products when genetic materials are under chemical/physical assault. 1,5,6 In particular, a class of DPCs has been shown to form between a prevalent DNA modification, abasic (AP) sites, 7 and lysine residues on interacting proteins via Schiff base chemistry. 8 DPCs derived from AP or oxidized AP sites have been demonstrated with DNA repair proteins, 9,10 nucleosome core particles, 11,12 and a transcription factor in mitochondria.…”

Section: ■ Introductionmentioning

confidence: 99%

“…DNA–protein interactions are essential to all aspects of genetic information transfer in living organisms, such as replication, transcription, recombination, and repair . Covalent DNA–protein cross-links (DPCs) mediated by chemical linkers serve as useful tools to map these interactions. − DPCs also form in biological contexts as intermediates during enzymatic processing of DNA or as products when genetic materials are under chemical/physical assault. ,, In particular, a class of DPCs has been shown to form between a prevalent DNA modification, abasic (AP) sites, and lysine residues on interacting proteins via Schiff base chemistry . DPCs derived from AP or oxidized AP sites have been demonstrated with DNA repair proteins, , nucleosome core particles, , and a transcription factor in mitochondria .…”

Section: Introductionmentioning

confidence: 99%

High-Resolution Mapping of Amino Acid Residues in DNA–Protein Cross-Links Enabled by Ribonucleotide-Containing DNA

et al. 2021

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DNA−protein cross-links have broad applications in mapping DNA−protein interactions and provide structural insights into macromolecular structures. However, high-resolution mapping of DNA-interacting amino acid residues with tandem mass spectrometry remains challenging due to difficulties in sample preparation and data analysis. Herein, we developed a method for identifying cross-linking amino residues in DNA−protein crosslinks at single amino acid resolution. We leveraged the alkaline lability of ribonucleotides and designed ribonucleotide-containing DNA to produce structurally defined nucleic acid−peptide crosslinks under our optimized ribonucleotide cleavage conditions. The structurally defined oligonucleotide−peptide heteroconjugates improved ionization, reduced the database search space, and facilitated the identification of cross-linking residues in peptides. We applied the workflow to identifying abasic (AP) site-interacting residues in human mitochondrial transcription factor A (TFAM)-DNA cross-links. With sub-nmol sample input, we obtained highquality fragmentation spectra for nucleic acid−peptide cross-links and identified 14 cross-linked lysine residues with the home-built AP_CrosslinkFinder program. Semi-quantification based on integrated peak areas revealed that K186 of TFAM is the major crosslinking residue, consistent with K186 being the closest (to the AP modification) lysine residue in solved TFAM:DNA crystal structures. Additional cross-linking lysine residues (K69, K76, K136, K154) support the dynamic characteristics of TFAM:DNA complexes. Overall, our combined workflow using ribonucleotide as a chemically cleavable DNA modification together with optimized sample preparation and data analysis offers a simple yet powerful approach for mapping cross-linking sites in DNA− protein cross-links. The method is amendable to other chemical or photo-cross-linking systems and can be extended to complex biological samples.

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“…DPCs are diverse lesions and can be classified on the basis of the crosslinked protein and the chemistry of the crosslink. Here, we provide a broad overview on DPC classification and direct the readers to references ( Stingele and Jentsch, 2015 ; Fielden et al, 2018 ; Sun et al, 2020a ; Wei et al, 2021 ; Weickert and Stingele, 2022 ) for more detailed DPC classification. Based on the identity of the crosslinked protein, DPCs are broadly classified into two groups: enzymatic and non-enzymatic.…”

Section: Dna-protein Crosslinksmentioning

confidence: 99%

“…In addition to utilizing components of canonical DNA repair pathways, tyrosyl-DNA phosphodiesterase 1 and 2 (TDP1 and TDP2) have been shown to mediate TOP1-cc and TOP2-cc repair, respectively ( Yang et al, 1996 ; Pouliot et al, 1999 ; Ledesma et al, 2009 ; Zeng et al, 2011 ). We refer the readers to excellent review articles that describe replication-independent DPC repair by NER, HR, MRE11, TDP1 and TDP2 in detail ( Sun et al, 2020a ; Sun et al, 2020b ; Wei et al, 2021 ; Weickert and Stingele, 2022 ). In this section we will discuss proteolysis of DPCs outside of S phase.…”

Section: Replication-independent Dpc Removalmentioning

confidence: 99%

Mechanisms and Regulation of DNA-Protein Crosslink Repair During DNA Replication by SPRTN Protease

Perry

Ghosal

2022

Front. Mol. Biosci.

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DNA-protein crosslinks (DPCs) are deleterious DNA lesions that occur when proteins are covalently crosslinked to the DNA by the action of variety of agents like reactive oxygen species, aldehydes and metabolites, radiation, and chemotherapeutic drugs. Unrepaired DPCs are blockades to all DNA metabolic processes. Specifically, during DNA replication, replication forks stall at DPCs and are vulnerable to fork collapse, causing DNA breakage leading to genome instability and cancer. Replication-coupled DPC repair involves DPC degradation by proteases such as SPRTN or the proteasome and the subsequent removal of DNA-peptide adducts by nucleases and canonical DNA repair pathways. SPRTN is a DNA-dependent metalloprotease that cleaves DPC substrates in a sequence-independent manner and is also required for translesion DNA synthesis following DPC degradation. Biallelic mutations in SPRTN cause Ruijs-Aalfs (RJALS) syndrome, characterized by hepatocellular carcinoma and segmental progeria, indicating the critical role for SPRTN and DPC repair pathway in genome maintenance. In this review, we will discuss the mechanism of replication-coupled DPC repair, regulation of SPRTN function and its implications in human disease and cancer.

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Mechanisms of DNA−protein cross-link formation and repair

Cited by 19 publications

References 94 publications

In vitro eradication of abasic site-mediated DNA–peptide/protein cross-links by Escherichia coli long-patch base excision repair

In vitro eradication of abasic site-mediated DNA–peptide/protein cross-links by Escherichia coli long-patch base excision repair

High-Resolution Mapping of Amino Acid Residues in DNA–Protein Cross-Links Enabled by Ribonucleotide-Containing DNA

Mechanisms and Regulation of DNA-Protein Crosslink Repair During DNA Replication by SPRTN Protease

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