Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation

Science. 2016 Sep 30;353(6307):1549-1552. doi: 10.1126/science.aaf7463.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • Centrosome / metabolism
  • Chromosomal Instability*
  • Cyclin A2 / genetics
  • Cyclin A2 / metabolism*
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA Repair Enzymes / genetics*
  • DNA Replication / genetics*
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation*
  • Humans
  • Kinesins / metabolism
  • MRE11 Homologue Protein
  • Meiosis / genetics
  • Mice
  • Mice, Mutant Strains
  • Mitosis / genetics
  • Protein Biosynthesis / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • S Phase / genetics


  • CCNA2 protein, mouse
  • Cyclin A2
  • DNA-Binding Proteins
  • Mre11a protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • CDC2 Protein Kinase
  • MRE11 Homologue Protein
  • Kif11 protein, mouse
  • Kinesins
  • DNA Repair Enzymes