Asset Details
Do you wish to reserve the book?
Proximity labeling identifies a repertoire of site-specific R-loop modulators
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Proximity labeling identifies a repertoire of site-specific R-loop modulators
Do you wish to request the book?
Proximity labeling identifies a repertoire of site-specific R-loop modulators
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Proximity labeling identifies a repertoire of site-specific R-loop modulators
2022
Overview
R-loops are three-stranded nucleic acid structures that accumulate on chromatin in neurological diseases and cancers and contribute to genome instability. Using a proximity-dependent labeling system, we identified distinct classes of proteins that regulate R-loops in vivo through different mechanisms. We show that ATRX suppresses R-loops by interacting with RNAs and preventing R-loop formation. Our proteomics screen also discovered an unexpected enrichment for proteins containing zinc fingers and homeodomains. One of the most consistently enriched proteins was activity-dependent neuroprotective protein (ADNP), which is frequently mutated in ASD and causal in ADNP syndrome. We find that ADNP resolves R-loops in vitro and that it is necessary to suppress R-loops in vivo at its genomic targets. Furthermore, deletion of the ADNP homeodomain severely diminishes R-loop resolution activity in vitro, results in R-loop accumulation at ADNP targets, and compromises neuronal differentiation. Notably, patient-derived human induced pluripotent stem cells that contain an ADNP syndrome-causing mutation exhibit R-loop and CTCF accumulation at ADNP targets. Our findings point to a specific role for ADNP-mediated R-loop resolution in physiological and pathological neuronal function and, more broadly, to a role for zinc finger and homeodomain proteins in R-loop regulation, with important implications for developmental disorders and cancers.
R-loops are three-stranded nucleic acid structures that contribute to genome instability and accumulate in neurological diseases. Here the authors identify R-loop proximal factors, which are enriched for zinc finger and homeodomain proteins, including activity-dependent neuroprotective protein (ADNP). ADNP plays a role in R-loop resolution and loss-of-function leads to R-loop accumulation.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/100
/ 45
/ 82/58
/ 82/80
/ Animals
/ Cancer
/ Genomes
/ Homeobox
/ Homeodomain Proteins - chemistry
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Induced Pluripotent Stem Cells
/ Labeling
/ Mice
/ Mutation
/ Nerve Tissue Proteins - chemistry
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Proteins
/ R-Loop Structures - genetics
/ R-Loop Structures - physiology
/ R-loops
/ Science
/ Zinc
