Редактирование: RRM2

Ribonucleoside-diphosphate reductase subunit M2 (EC 1.17.4.1) (Ribonucleotide reductase small chain) (Ribonucleotide reductase small subunit) [RR2]

==Publications==

{{medline-entry
|title=Increased Rrm2 gene dosage reduces fragile site breakage and prolongs survival of [[ATR]] mutant mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25838540
|abstract=In Saccharomyces cerevisiae, absence of the checkpoint kinase Mec1 ([[ATR]]) is viable upon mutations that increase the activity of the ribonucleotide reductase (RNR) complex. Whether this pathway is conserved in mammals remains unknown. Here we show that cells from mice carrying extra alleles of the RNR regulatory subunit [[RRM2]] (Rrm2(TG)) present supraphysiological RNR activity and reduced chromosomal breakage at fragile sites. Moreover, increased Rrm2 gene dosage significantly extends the life span of [[ATR]] mutant mice. Our study reveals the first genetic condition in mammals that reduces fragile site expression and alleviates the severity of a progeroid disease by increasing RNR activity.
|mesh-terms=* Animals
* Cell Line
* Cell Survival
* Cells, Cultured
* Chromosome Breakage
* Chromosome Fragile Sites
* Enzyme Activation
* Fibroblasts
* Gene Dosage
* Humans
* Longevity
* Mice
* Nucleosides
* Protein-Serine-Threonine Kinases
* Ribonucleoside Diphosphate Reductase
* Survival Analysis
|keywords=* ATR
* RNR
* fragile site
* mouse models
* replication stress
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387711
}}
{{medline-entry
|title=Identification of ribonucleotide reductase M2 as a potential target for pro-senescence therapy in epithelial ovarian cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24200970
|abstract=Epithelial ovarian cancer (EOC) is the leading cause of gynecological-related cancer deaths in the United States. There is, therefore, an urgent need to develop novel therapeutic strategies for this devastating disease. Cellular senescence is a state of stable cell growth arrest that acts as an important tumor suppression mechanism. Ribonucleotide reductase M2 ([[RRM2]]) plays a key role in regulating the senescence-associated cell growth arrest by controlling biogenesis of 2'-deoxyribonucleoside 5'-triphosphates (dNTPs). The role of [[RRM2]] in EOC remains poorly understood. Here we show that [[RRM2]] is expressed at higher levels in EOCs compared with either normal ovarian surface epithelium (P<0.001) or fallopian tube epithelium (P<0.001). [[RRM2]] expression significantly correlates with the expression of Ki67, a marker of cell proliferation (P<0.001). Moreover, [[RRM2]] expression positively correlates with tumor grade and stage, and high [[RRM2]] expression independently predicts a shorter overall survival in EOC patients (P<0.001). To delineate the functional role of [[RRM2]] in EOC, we knocked down [[RRM2]] expression in a panel of EOC cell lines. Knockdown of [[RRM2]] expression inhibits the growth of human EOC cells. Mechanistically, [[RRM2]] knockdown triggers cellular senescence in these cells. Notably, this correlates with the induction of the DNA damage response, a known mediator of cellular senescence. These data suggest that targeting [[RRM2]] in EOCs by suppressing its activity is a novel pro-senescence therapeutic strategy that has the potential to improve survival of EOC patients. 
|mesh-terms=* Carcinoma, Ovarian Epithelial
* Cell Line, Tumor
* Cell Proliferation
* Cellular Senescence
* DNA Damage
* Epithelium
* Fallopian Tubes
* Female
* Gene Knockdown Techniques
* Humans
* Ki-67 Antigen
* Middle Aged
* Molecular Targeted Therapy
* Neoplasm Grading
* Neoplasm Staging
* Neoplasms, Glandular and Epithelial
* Ovarian Neoplasms
* Ovary
* Ribonucleoside Diphosphate Reductase
* Survival Rate
|keywords=* DNA damage response
* cell proliferation
* cellular senescence
* epithelial ovarian cancer
* ribonucleotide reductase M2 (RRM2)
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906237
}}
{{medline-entry
|title=Age-specific gene expression signatures for breast tumors and cross-species conserved potential cancer progression markers in young women.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23704896
|abstract=Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, [[CCNB2]], [[UBE2C]], [[TOP2A]], [[CEP55]], [[TPX2]], [[BIRC5]], KIAA0101, [[SHCBP1]], [[UBE2T]], [[PTTG1]], [[NUSAP1]], [[DEPDC1]], [[HELLS]], [[CCNB1]], [[KIF4A]], and [[RRM2]], that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
|mesh-terms=* Adult
* Aging
* Animals
* Biomarkers, Tumor
* Breast Neoplasms
* Carcinogenesis
* Carcinoma, Ductal, Breast
* Carcinoma, Intraductal, Noninfiltrating
* Cohort Studies
* Computational Biology
* Disease Progression
* Female
* Gene Expression Regulation, Neoplastic
* Gene Regulatory Networks
* Genes, Neoplasm
* Genome, Human
* Humans
* Immunohistochemistry
* Mice
* Middle Aged
* Oligonucleotide Array Sequence Analysis
* Reproducibility of Results
* Species Specificity
* Transcriptome
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660335
}}