Cell cycle regulation and RNA polymerase II

The cell cycle and transcription by RNA polymerase II (RNAP II) are closely related. They utilize shared components. RNAP II transcriptional activity is modulated during the cell cycle. Cell cycle dependent changes in the pho sphorylation status of the carboxyl-terminal domain (CTD) of the largest su bunit of RNAP II (RNAP II-LS) alter transcription. Several CTD kinases are members of the cyclin-dependent kinase (cdk) superfamily, including p34(cdc 2) (cdk1), cdk7, cdk8, and cdk9. Each of these cdks, with their respective cyclin partners, have been linked to cell cycle regulatory events. Other CT D kinases such as casein kinase II (CKII) and c-abl have also been implicat ed in cell cycle dependent modifications of the CTD. In addition, the stall ing of RNAP II complexes at DNA lesions helps stimulate p53 accumulation wh ich largely determines the cell's DNA damage response, including cell cycle arrest. Alzheimer's disease pathology results partially from activation of mitotic cdks in postmitotic neurons which can phosphorylate RNAP II-LS and other targets.