Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F15%3A00080745" target="_blank" >RIV/00216224:14740/15:00080745 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/15:00446324

Result on the web

<a href="http://nar.oxfordjournals.org/content/43/5/2575" target="_blank" >http://nar.oxfordjournals.org/content/43/5/2575</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/nar/gkv101" target="_blank" >10.1093/nar/gkv101</a>

Result language

angličtina

Original language name

Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex.

Original language description

The Cdk12/CycK complex promotes expression of a subset of RNA polymerase II genes, including those of the DNA damage response. CDK12 is among only nine genes with recurrent somatic mutations in high-grade serous ovarian carcinoma. However, the influenceof thesemutations on the Cdk12/CycK complex and their link to cancerogenesis remain ill-defined. Here, we show that most mutations prevent formation of the Cdk12/CycK complex, rendering the kinase inactive. By examining the mutations within the Cdk12/CycK structure, we find that they likely provoke structural rearrangements detrimental to Cdk12 activation. Our mRNA expression analysis of the patient samples containing the CDK12 mutations reveals coordinated downregulation of genes critical to the homologous recombination DNA repair pathway. Moreover, we establish that the Cdk12/CycK complex occupies these genes and promotes phosphorylation of RNA polymerase II at Ser2.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nucleic Acids Research

ISSN

0305-1048

e-ISSN

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Volume of the periodical

43

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

2575-2589

UT code for WoS article

000352487100015

EID of the result in the Scopus database

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