eprintid: 10098932
rev_number: 15
eprint_status: archive
userid: 608
dir: disk0/10/09/89/32
datestamp: 2020-06-01 09:14:37
lastmod: 2021-10-14 22:58:13
status_changed: 2020-06-01 09:14:37
type: article
metadata_visibility: show
creators_name: Gajduskova, P
creators_name: Ruiz de los Mozos, I
creators_name: Rajecky, M
creators_name: Hluchy, M
creators_name: Ule, J
creators_name: Blazek, D
title: CDK11 is required for transcription of replication-dependent histone genes
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F85
divisions: C08
divisions: D09
divisions: F99
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Replication-dependent histones (RDH) are required for packaging of newly synthetized DNA into nucleosomes during the S phase when their expression is highly upregulated. However, the mechanisms of this upregulation in metazoan cells remain poorly understood. Using iCLIP and ChIP–seq, we found that human cyclin-dependent kinase 11 (CDK11) associates with RNA and chromatin of RDH genes primarily in the S phase. Moreover, its amino-terminal region binds FLASH, an RDH-specific 3′-end processing factor, which keeps the kinase on the chromatin. CDK11 phosphorylates serine 2 (Ser2) of the carboxy-terminal domain of RNA polymerase II (RNAPII), which is initiated when RNAPII reaches the middle of RDH genes and is required for further RNAPII elongation and 3′-end processing. CDK11 depletion leads to decreased number of cells in S phase, likely owing to the function of CDK11 in RDH gene expression. Thus, the reliance of RDH expression on CDK11 could explain why CDK11 is essential for the growth of many cancers.
date: 2020-05-04
date_type: published
publisher: NATURE PUBLISHING GROUP
official_url: http://dx.doi.org/10.1038/s41594-020-0406-8
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1780842
doi: 10.1038/s41594-020-0406-8
lyricists_name: Ruiz De Los Mozos, Igor
lyricists_name: Ule, Jernej
lyricists_id: IRUIZ81
lyricists_id: JULEX61
actors_name: Ule, Jernej
actors_id: JULEX61
actors_role: owner
full_text_status: public
publication: Nature Structural and Molecular Biology
volume: 27
pagerange: 500-510
pages: 33
citation:        Gajduskova, P;    Ruiz de los Mozos, I;    Rajecky, M;    Hluchy, M;    Ule, J;    Blazek, D;      (2020)    CDK11 is required for transcription of replication-dependent histone genes.                   Nature Structural and Molecular Biology , 27    pp. 500-510.    10.1038/s41594-020-0406-8 <https://doi.org/10.1038/s41594-020-0406-8>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10098932/1/34564_2_merged_1583332566.pdf