Cyclin K goes with Cdk12 and Cdk13

The family of cyclin-dependent kinases (Cdks) consists of 21 proteins whose activities usually require association with a specific cyclin subunit [1]. The first Cdks to be described were regulators of the cell cycle, such as Cdk1, Cdk2, Cdk4, and Cdk6. Their corresponding cyclins are also the most well characterized [2,3]. Another group of cyclin/Cdk complexes, including cyclin H/Cdk7 and cyclin T/Cdk9, have cell cycle-independent activities. These complexes are engaged in the regulation of transcription and posttrancriptional mRNA processing via the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) and other transcriptional regulators, such as DRB (5,6-dichloro-1-？-D-ribofuranosylbenzimidazole) sensitivity inducing factor (DSIF) or negative elongation factor (NELF) [4]. Recent work led to the characterization of new transcription cycle-related Cdk complexes: cyclin K/cyclin-dependent kinase 12 (CycK/Cdk12) and CycK/Cdk13 [5,6]. In addition, it has been shown that CycK/Cdk12 maintains genome stability by regulating the expression of several important DNA damage response (DDR) genes [5,7]. These findings were fueled by recent developments in the field of RNAPII-mediated transcription that led to: 1) increased interest in the elucidation of the CTD code [4,8]; 2) the finding that promoter-paused RNAPII and elongation represent important regulatory steps in gene expression [9,10]; 3) the conclusion that phosphorylation of the CTD couples transcription to other cellular processes [11-13]; and 4) clarification of the relationship between what was considered to be the only human serine 2 (Ser2) CTD kinase, Cdk9, and its two putative yeast homologs, Bur1 and Ctk1 [6,14].Human CycK was first identified as a protein that can rescue the lethality caused by deletion of the G1 cyclin genes CLN1, CLN2, and CLN3 in Saccharomyces cerevisiae [15]. It was discovered as a 40-kDa and 357-amino acid protein whose mRNA is ubiquitously expressed in all tested h