2021
DOI: 10.1038/s41557-021-00736-9
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Chemical profiling of DNA G-quadruplex-interacting proteins in live cells

Abstract: DNA–protein interactions regulate critical biological processes. Identifying proteins that bind to specific, functional genomic loci is essential to understand the underlying regulatory mechanisms on a molecular level. Here we describe a co-binding-mediated protein profiling (CMPP) strategy to investigate the interactome of DNA G-quadruplexes (G4s) in native chromatin. CMPP involves cell-permeable, functionalized G4-ligand probes that bind endogenous G4s and subsequently crosslink to co-binding G4-interacting … Show more

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Cited by 95 publications
(98 citation statements)
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References 72 publications
(106 reference statements)
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“…End-resection is one of the first steps during HR that is mainly mediated by exonuclease 1 (EXO1) [105]. It has been shown in human cells that EXO1 is important for replication and resection near G4 structures [69]. Besides EXO1, DNA2 functions in the initiation of homology-mediated DSB repair by generating 3 ssDNA overhangs [106][107][108].…”
Section: Pathwaymentioning
confidence: 99%
“…End-resection is one of the first steps during HR that is mainly mediated by exonuclease 1 (EXO1) [105]. It has been shown in human cells that EXO1 is important for replication and resection near G4 structures [69]. Besides EXO1, DNA2 functions in the initiation of homology-mediated DSB repair by generating 3 ssDNA overhangs [106][107][108].…”
Section: Pathwaymentioning
confidence: 99%
“…It can also resolve the 5′-UTR G4 RNA to regulate MAGE family member D2 (MAGED2) protein level ( McRae et al, 2020 ) and the 3′-UTR G4 RNA to suppress gene expression ( McRae et al, 2017 ). Most recently, DDX1, DDX24, DDX42, and DDX58 were identified to bind G4 DNA or RNA; however, the cellular functions are still elusive ( Zyner et al, 2019 ; Herviou et al, 2020 ; Zhang X. et al, 2021 ).…”
Section: G-quadruplex Unwinding Helicases and Their Functionsmentioning
confidence: 99%
“…Taken together, these studies provide compelling evidence to further identify and investigate other DDX helicase genes and associated alterations that may drive cancer through perturbations of the genome. For example, DDX42 and DDX50 were found to be PARP1 interactors, DDX26B is a core subunit of the integrator transcriptional complex enriched at UV damage sites, and DDX24 was found to interact with G4 quadruplex DNA [89][90][91]. DNA G4-quadruplex structures may underpin DDX helicase transcription initiation mechanisms and/or stabilize R-loop structures [92,93].…”
Section: Discussionmentioning
confidence: 99%