PXD018207

PXD018207 is an original dataset announced via ProteomeXchange.

Title	ATAD5 regulates R-loop by maintaining RNA helicase level and unloading PCNA at the replication fork
Description	R-loops are formed when replicative forks collide with the transcriptional machinery and can cause genomic instability. However, it is unclear how R-loops are regulated at transcription-replication conflicts (TRC) sites and how replisome proteins are regulated to prevent R-loop formation or mediate R-loop tolerance. Here, we report that ATAD5, a PCNA unloader, plays dual functions to reduce R-loops both under normal and replication stress conditions. ATAD5 interacts with RNA helicases such as DDX1, DDX5, DDX21 and DHX9 and increases the abundance of these helicases at replication forks to facilitate R-loop resolution. Depletion of ATAD5 or RNA helicases consistently increases R-loops during the S phase and reduces the replication rate, both of which are enhanced by replication stress. In addition to R-loop resolution, ATAD5 prevents the generation of new R-loops behind the replication forks by unloading PCNA which, otherwise, accumulates and persists on DNA, causing a collision with the transcription machinery. Depletion of ATAD5 reduces transcription rates due to PCNA accumulation. Consistent with the role of ATAD5 and RNA helicases in maintaining genomic integrity by regulating R-loops, the corresponding genes were mutated or downregulated in several human tumors.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:27:58.244.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Byung-gyu kim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-25 23:52:42	ID requested
1	2021-09-09 00:27:36	announced
⏵ 2	2024-10-22 05:27:59	announced	2024-10-22: Updated project metadata.

10.1093/nar/gkaa501;

Kim S, Kang N, Park SH, Wells J, Hwang T, Ryu E, Kim BG, Hwang S, Kim SJ, Kang S, Lee S, Stirling P, Myung K, Lee KY, ATAD5 restricts R-loop formation through PCNA unloading and RNA helicase maintenance at the replication fork. Nucleic Acids Res, 48(13):7218-7238(2020) [pubmed]

submitter keyword: DEAD-box RNA helicase,ATAD5, R-loop, Replication stress, PCNA

Kyoo-young Lee
contact affiliation	Center for Genomic Integrity, Institute for Basic Science, Ulsan, Korea
contact email	klee2910@ibs.re.kr
lab head
Byung-gyu kim
contact affiliation	Center for genomic integrity (CGI), Institute of basic science (IBS), UNIST, Ulsan, 44919, Republic of Korea
contact email	goldenlion@ibs.re.kr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD018207

PRIDE project URI

• PRIDE
  1. PXD018207
     1. Label: PRIDE project
     2. Name: ATAD5 regulates R-loop by maintaining RNA helicase level and unloading PCNA at the replication fork