Citations 1
Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation
Jeganathan, Karthik B. , Limzerwala, Jazeel F. , Baker, Darren J. , Hamada, Masakazu , Nam, Hyun-Ja, Deursen, Willemijn H. van , Hamada, Naomi, Naylor, Ryan M. , Becker, Nicole A. , Davies, Brian A., Ree, Janine H. van, Mer, Georges , Maher, L. James, Katzmann, David J. , Deursen, Jan M. van , Kanakkanthara, Arun , van Deursen, Willemijn H, van Ree, Janine H, Shapiro, Virginia S, Hamada, Masakazu, Shapiro, Virginia Smith , Jeganathan, Karthik B , Baker, Darren J
Science | September 29, 2016 | Volume: 353 | Issue: 6307 | Pages: 1549-1552
Cyclin A2 activates the cyclin-dependent kinases Cdk1 and Cdk2 and is expressed at elevated levels from S phase until early mitosis. We found that mutant mice that cannot elevate cyclin A2 are chromosomally unstable and tumor-prone. Underlying the chromosomal instability is a failure to up-regulate the meiotic recombination 11 (Mre11) nuclease in S phase, which leads to impaired resolution of stalled replication forks, insufficient repair of double-stranded DNA breaks, and improper segregation of sister chromosomes. Unexpectedly, cyclin A2 controlled Mre11 abundance through a C-terminal RNA binding domain that selectively and directly binds Mre11 transcripts to mediate polysome loading and translation. These data reveal cyclin A2 as a mechanistically diverse regulator of DNA replication combining multifaceted kinase-dependent functions with a kinase-independent, RNA binding–dependent role that ensures adequate repair of common replication errors.