Increased tRNA modification and gene-specific codon usage regulate cell cycle progression during the DNA damage response.

ABSTRACT: S-phase and DNA damage promote increased ribonucleotide reductase (RNR) activity. Translation of RNR1 has been linked to the wobble uridine modifying enzyme tRNA methyltransferase 9 (Trm9). We predicted that changes in tRNA modification would translationally regulate RNR1 after DNA damage to promote cell cycle progression. In support, we demonstrate that the Trm9-dependent tRNA modification 5-methoxycarbonylmethyluridine (mcm(5)U) is increased in hydroxyurea (HU)-induced S-phase cells, relative to G(1) and G(2), and that mcm(5)U is one of 16 tRNA modifications whose levels oscillate during the cell cycle. Codon-reporter data matches the mcm(5)U increase to Trm9 and the efficient translation of AGA codons and RNR1. Further, we show that in trm9Δ cells reduced Rnr1 protein levels cause delay

SUBMITTER: Patil A 

PROVIDER: S-EPMC3478316 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature