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