Nature Communications (Apr 2019)
CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation
- Malgorzata Krajewska,
- Ruben Dries,
- Andrew V. Grassetti,
- Sofia Dust,
- Yang Gao,
- Hao Huang,
- Bandana Sharma,
- Daniel S. Day,
- Nicholas Kwiatkowski,
- Monica Pomaville,
- Oliver Dodd,
- Edmond Chipumuro,
- Tinghu Zhang,
- Arno L. Greenleaf,
- Guo-Cheng Yuan,
- Nathanael S. Gray,
- Richard A. Young,
- Matthias Geyer,
- Scott A. Gerber,
- Rani E. George
Affiliations
- Malgorzata Krajewska
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Ruben Dries
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Andrew V. Grassetti
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth
- Sofia Dust
- Institute of Structural Biology, University of Bonn
- Yang Gao
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Hao Huang
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Bandana Sharma
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Daniel S. Day
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- Nicholas Kwiatkowski
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Monica Pomaville
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Oliver Dodd
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Edmond Chipumuro
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- Tinghu Zhang
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Arno L. Greenleaf
- Department of Biochemistry, Duke University Medical Center
- Guo-Cheng Yuan
- Departments of Biostatistics and Computational Biology, Dana-Farber Cancer Institute
- Nathanael S. Gray
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Richard A. Young
- Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology
- Matthias Geyer
- Institute of Structural Biology, University of Bonn
- Scott A. Gerber
- Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth
- Rani E. George
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children’s Hospital
- DOI
- https://doi.org/10.1038/s41467-019-09703-y
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 16
Abstract
Cdk12 is primarily involved in the regulation of DNA damage response (DDR) gene transcription as well as mRNA processing. Here, the authors demonstrate that CDK12 suppresses intronic polyadenylation, and that inhibition of this kinase primarily affects the expression of long genes with higher numbers of polyA sites, features common to many DDR genes.
