Cyclin A2 is an RNA binding protein that controls Mre11 mRNA translation.
Science
; 353(6307): 1549-1552, 2016 09 30.
Article
em En
| MEDLINE
| ID: mdl-27708105
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biossíntese de Proteínas
/
RNA Mensageiro
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Regulação da Expressão Gênica
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Proteínas de Ligação a RNA
/
Instabilidade Cromossômica
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Enzimas Reparadoras do DNA
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Proteínas de Ligação a DNA
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Replicação do DNA
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Ciclina A2
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos