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@article{1652296,
author = {Gajdušková, Pavla and de los Mozos, I.R. and Rájecký, Michal and Hluchý, Milan and Ule, J. and Blažek, Dalibor},
article_number = {5},
doi = {http://dx.doi.org/10.1038/s41594-020-0406-8},
keywords = {RNA-POLYMERASE-II; TERMINAL DOMAIN; CELL-GROWTH; IN-VIVO; CTD; EXPRESSION; PROMOTES; IDENTIFICATION; THREONINE-4; COMPLEXES},
language = {eng},
issn = {1545-9993},
journal = {NATURE STRUCTURAL & MOLECULAR BIOLOGY},
title = {CDK11 is required for transcription of replication-dependent histone genes},
url = {https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D},
volume = {27},
year = {2020}
}
TY - JOUR
ID - 1652296
AU - Gajdušková, Pavla - de los Mozos, I.R. - Rájecký, Michal - Hluchý, Milan - Ule, J. - Blažek, Dalibor
PY - 2020
TI - CDK11 is required for transcription of replication-dependent histone genes
JF - NATURE STRUCTURAL & MOLECULAR BIOLOGY
VL - 27
IS - 5
SP - 500-510
EP - 500-510
SN - 15459993
KW - RNA-POLYMERASE-II
KW - TERMINAL DOMAIN
KW - CELL-GROWTH
KW - IN-VIVO
KW - CTD
KW - EXPRESSION
KW - PROMOTES
KW - IDENTIFICATION
KW - THREONINE-4
KW - COMPLEXES
UR - https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D
L2 - https://www.nature.com/articles/s41594-020-0406-8.epdf?sharing_token=zNiOaCgpJZhem_WElNA609RgN0jAjWel9jnR3ZoTv0OO1owaT10EcQ1vPi7szjqCsaEjWY2IQtiItuKeKjIpkAhzuhflNMAeLZP_WeA1awOJ31AKIJ5ExKjhfUxlDYBKXkDcyfl1Ct4MaGwK1m3yPunqKmM7hSCQeXqK3ylRHsM%3D
N2 - CDK11 functions with histone pre-mRNA-processing factor FLASH to upregulate expression of replication-dependent histone genes in S phase and to couple transcription and processing of nascent histone transcripts in mammalian cells. 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.
ER -
GAJDUŠKOVÁ, Pavla, I.R. DE LOS MOZOS, Michal RÁJECKÝ, Milan HLUCHÝ, J. ULE and Dalibor BLAŽEK. CDK11 is required for transcription of replication-dependent histone genes. \textit{NATURE STRUCTURAL \&{} MOLECULAR BIOLOGY}. 2020, vol.~27, No~5, p.~500-510, 33 pp. ISSN~1545-9993. Available from: https://dx.doi.org/10.1038/s41594-020-0406-8.
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