| First Author | Kanakkanthara A | Year | 2016 |
| Journal | Science | Volume | 353 |
| Issue | 6307 | Pages | 1549-1552 |
| PubMed ID | 27708105 | Mgi Jnum | J:235861 |
| Mgi Id | MGI:5803886 | Doi | 10.1126/science.aaf7463 |
| Citation | Kanakkanthara A, et al. (2016) Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation. Science 353(6307):1549-1552 |
| abstractText | 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. |
