We have examined the insertion of carbenes carrying leaving groups into the [nido-B11H13]2- dianion to form the [closo-1-CB11H12]- anion. The best procedure uses CF3SiMe3 and LiCl as the source of CF2. It is simple, convenient and scalable and proceeds with 70-90% yield. Density functional calculations have been used to develop a mechanistic proposal that accounts for the different behavior of CF2, requiring only one equivalent of base for successful conversion of Na[nido-B11H14]- to [closo-1-CB11H12]-, and CCl2 and CBr2, which require more.

• MeSH
• Lithium Chloride chemistry   MeSH
• Hydrocarbons, Fluorinated chemical synthesis   chemistry   MeSH
• Molecular Structure MeSH
• Boron Compounds chemistry   MeSH
• Publication type
• Journal Article MeSH

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.

• MeSH
• Cyclin-Dependent Kinases genetics   metabolism   MeSH
• Phosphorylation MeSH
• HCT116 Cells MeSH
• G1 Phase Cell Cycle Checkpoints genetics   physiology   MeSH
• Humans MeSH
• DNA Repair genetics   physiology   MeSH
• DNA Replication genetics   physiology   MeSH
• RNA Polymerase II genetics   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH