PXD000686

PXD000686 is an original dataset announced via ProteomeXchange.

Title	Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication
Description	During DNA replication, nucleosomes are rapidly assembled on newly synthesized DNA to restore chromatin organization. Asf1, a key histone H3-H4 chaperone required for this process, is phosphorylated by Tousled-Like Kinases (TLKs). Here, we identify TLK phosphorylation sites by mass spectrometry and dissect how phosphorylation impacts on human Asf1 function. The divergent C-terminal tail of Asf1a is phosphorylated at several sites and this is required for timely progression through S phase. Consistent with this, biochemical analysis of wild-type and phospho-mimetic Asf1a shows that phosphorylation enhances binding to histones and the downstream chaperones CAF-1 and HIRA. Moreover, we find that TLK phosphorylation of Asf1a is induced in cells experiencing deficiency of new histones and that TLK interaction with Asf1a involves its histone-binding pocket. We thus propose that TLK signaling promotes histone supply in S phase by targeting histone-free Asf1 and stimulating its ability to shuttle histones to sites of chromatin assembly.
HostingRepository	PRIDE
AnnounceDate	2014-07-24
AnnouncementXML	Submission_2014-07-24_03:48:34.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Clifford Young
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; phosphorylated residue; N-acetylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2014-01-16 01:01:41	ID requested
1	2014-03-06 05:17:18	announced
2	2014-03-10 06:51:32	announced	Updated publication reference for PubMed record(s): 24598821.
⏵ 3	2014-07-24 03:48:35	announced	Updated project metadata.

Klimovskaia IM, Young C, Str, ø, mme CB, Menard P, Jasencakova Z, Mejlvang J, Ask K, Ploug M, Nielsen ML, Jensen ON, Groth A, Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication. Nat Commun, 5():3394(2014) [pubmed]

curator keyword: Biological

submitter keyword: Asf1a, Asf1b, phosphopeptide, thermolysin

Ole Nørregaard Jensen
contact affiliation	Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
contact email	jenseno@bmb.sdu.dk
lab head
Clifford Young
contact affiliation	Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Denmark.
contact email	clifford.young@cpr.ku.dk
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/2014/03/PXD000686

PRIDE project URI

• PRIDE
  1. PXD000686
     1. Label: PRIDE project
     2. Name: Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication