| CHIRACKAL MANAVALAN, Anil Paul, Květa PILAŘOVÁ, Michael KLUGE, Koen BARTHOLOMEEUSEN, Michal RÁJECKÝ, Jan OPPELT, PrashantKumar KHIRSARIYA, Kamil PARUCH, Lumír KREJČÍ, Caroline C FRIEDEL and Dalibor BLAŽEK. CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes. EMBO reports. Hoboken: Wiley-Blackwell, 2019, vol. 20, No 9, p. 1-29. ISSN 1469-221X. Available from: https://dx.doi.org/10.15252/embr.201847592. |
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@article{1576236,
author = {Chirackal Manavalan, Anil Paul and Pilařová, Květa and Kluge, Michael and Bartholomeeusen, Koen and Rájecký, Michal and Oppelt, Jan and Khirsariya, PrashantKumar and Paruch, Kamil and Krejčí, Lumír and Friedel, Caroline C and Blažek, Dalibor},
article_location = {Hoboken},
article_number = {9},
doi = {http://dx.doi.org/10.15252/embr.201847592},
keywords = {CDK12; G1; S; CTD Ser2 phosphorylation; premature termination and polyadenylation; tandem duplications},
language = {eng},
issn = {1469-221X},
journal = {EMBO reports},
title = {CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes},
url = {https://www.embopress.org/doi/full/10.15252/embr.201847592},
volume = {20},
year = {2019}
}
TY - JOUR
ID - 1576236
AU - Chirackal Manavalan, Anil Paul - Pilařová, Květa - Kluge, Michael - Bartholomeeusen, Koen - Rájecký, Michal - Oppelt, Jan - Khirsariya, PrashantKumar - Paruch, Kamil - Krejčí, Lumír - Friedel, Caroline C - Blažek, Dalibor
PY - 2019
TI - CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes
JF - EMBO reports
VL - 20
IS - 9
SP - 1-29
EP - 1-29
PB - Wiley-Blackwell
SN - 1469221X
KW - CDK12
KW - G1
KW - S
KW - CTD Ser2 phosphorylation
KW - premature termination and polyadenylation
KW - tandem duplications
UR - https://www.embopress.org/doi/full/10.15252/embr.201847592
L2 - https://www.embopress.org/doi/full/10.15252/embr.201847592
N2 - CDK12 is a kinase associated with elongating RNA polymerase II (RNAPII) and is frequently mutated in cancer. CDK12 depletion reduces the expression of homologous recombination (HR) DNA repair genes, but comprehensive insight into its target genes and cellular processes is lacking. We use a chemical genetic approach to inhibit analog-sensitive CDK12, and find that CDK12 kinase activity is required for transcription of core DNA replication genes and thus for G1/S progression. RNA-seq and ChIP-seq reveal that CDK12 inhibition triggers an RNAPII processivity defect characterized by a loss of mapped reads from 3 ' ends of predominantly long, poly(A)-signal-rich genes. CDK12 inhibition does not globally reduce levels of RNAPII-Ser2 phosphorylation. However, individual CDK12-dependent genes show a shift of P-Ser2 peaks into the gene body approximately to the positions where RNAPII occupancy and transcription were lost. Thus, CDK12 catalytic activity represents a novel link between regulation of transcription and cell cycle progression. We propose that DNA replication and HR DNA repair defects as a consequence of CDK12 inactivation underlie the genome instability phenotype observed in many cancers.
ER -
CHIRACKAL MANAVALAN, Anil Paul, Květa PILAŘOVÁ, Michael KLUGE, Koen BARTHOLOMEEUSEN, Michal RÁJECKÝ, Jan OPPELT, PrashantKumar KHIRSARIYA, Kamil PARUCH, Lumír KREJČÍ, Caroline C FRIEDEL and Dalibor BLAŽEK. CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes. \textit{EMBO reports}. Hoboken: Wiley-Blackwell, 2019, vol.~20, No~9, p.~1-29. ISSN~1469-221X. Available from: https://dx.doi.org/10.15252/embr.201847592.
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