Details

Autor(en) / Beteiligte

• Kanakkanthara, Arun
• Jeganathan, Karthik B
• Limzerwala, Jazeel F
• Baker, Darren J
• Hamada, Masakazu
• Nam, Hyun-Ja
• van Deursen, Willemijn H
• Hamada, Naomi
• Naylor, Ryan M
• Becker, Nicole A
• Davies, Brian A
• van Ree, Janine H
• Mer, Georges
• Shapiro, Virginia S
• Maher, 3rd, L James
• Katzmann, David J
• van Deursen, Jan M

Titel

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

Ist Teil von

• Science (American Association for the Advancement of Science), 2016-09, Vol.353 (6307), p.1549-1552

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2016

Quelle

American Association for the Advancement of Science

Beschreibungen/Notizen

• 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.