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Cell senescence database
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Basic Information

Gene ID

6240

Name

RRM1

Synonymous

ribonucleotide reductase M1;RRM1;ribonucleotide reductase M1

Definition

ribonucleoside-diphosphate reductase large subunit|ribonucleoside-diphosphate reductase subunit M1|ribonucleotide reductase M1 polypeptide|ribonucleotide reductase, R1 subunit

Position

11p15.5

Gene type

protein-coding

Title

Abstract

Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C-MYC depletion.

The down-regulation of dominant oncogenes, including C-MYC, in tumor cells often leads to the induction of senescence via mechanisms that are not completely identified. In the current study, we demonstrate that MYC-depleted melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase (TS) and ribonucleotide reductase (RR) and subsequent depletion of deoxyribonucleoside triphosphate pools. Simultaneous genetic inhibition of TS and RR in melanoma cells induced DNA damage and senescence phenotypes very similar to the ones caused by MYC-depletion. Reciprocally, overexpression of TS and RR in melanoma cells or addition of deoxyribo-nucleosides to culture media substantially inhibited DNA damage and senescence-associated phenotypes caused by C-MYC depletion. Our data demonstrate the essential role of TS and RR in C-MYC-dependent suppression of senescence in melanoma cells.

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