Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maintenance of a genome requires DNA repair integrated with chromatin remodeling. We have analyzed six transcriptome data sets and one data set on translational regulation of known DNA repair and remodeling genes in synchronized human cells. These data are available through our new database: www.dnarepairgenes.com. Genes that have similar transcription profiles in at least two of our data sets generally agree well with known protein profiles. In brief, long patch base excision repair (BER) is enriched for S phase genes, whereas short patch BER uses genes essentially equally expressed in all cell cycle phases. Furthermore, most genes related to DNA mismatch repair, Fanconi anemia and homologous recombination have their highest expression in the S phase. In contrast, genes specific for direct repair, nucleotide excision repair, as well as non-homologous end joining do not show cell cycle-related expression. Cell cycle regulated chromatin remodeling genes were most frequently confined to G1/S and S. These include e.g. genes for chromatin assembly factor 1 (CAF-1) major subunits CHAF1A and CHAF1B; the putative helicases HELLS and ATAD2 that both co-activate E2F transcription factors central in G1/S-transition and recruit DNA repair and chromatin-modifying proteins and DNA double strand break repair proteins; and RAD54L and RAD54B involved in double strand break repair. TOP2A was consistently most highly expressed in G2, but also expressed in late S phase, supporting a role in regulating entry into mitosis. Translational regulation complements transcriptional regulation and appears to be a relatively common cell cycle regulatory mechanism for DNA repair genes. Our results identify cell cycle phases in which different pathways have highest activity, and demonstrate that periodically expressed genes in a pathway are frequently co-expressed. Furthermore, the data suggest that S phase expression and over-expression of some multifunctional chromatin remodeling proteins may set up feedback loops driving cancer cell proliferation.
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PMID:Cell cycle regulation of human DNA repair and chromatin remodeling genes. 2588 Oct 42

Sepantronium bromide (YM-155) is believed to elicit apoptosis and mitotic arrest in tumor cells by reducing (BIRC5, survivin) mRNA. In this study, we monitored changes in survivin mRNA and protein after treating MDA-MB-231 cells with YM-155 concurrent with evaluation of whole transcriptomic (WT) mRNA and long intergenic non-coding RNA at 2 time points: 8 h sub-lethal (83 ng/mL) and 20 h at the LC50 (14.6 ng/mL). The data show a tight association between cell death and the precipitating loss of survivin protein and mRNA (-2.67 fold-change (FC), p<0.001) at 20 h, questioning if the decline in survivin is attributed to cell death or drug impact. The meager loss of survivin mRNA was overshadowed by enormous differential change to the WT in both magnitude and significance for over 2000 differentially up/down-regulated transcripts: (+22 FC to -12 FC, p<0.001). The data show YM-155 to up-regulate transcripts in control of circadian rhythm (NOCT, PER, BHLHe40, NFIL3), tumor suppression (SIK1, FOSB), histone methylation (KDM6B) and negative feedback of NF-kappa B signaling (TNFAIP3). Down-regulated transcripts by YM-155 include glucuronidase (GUSBP3), numerous micro-RNAs, DNA damage repair elements (CENPI, POLQ, RAD54B) and the most affected system was the ataxia-telangiectasia mutated (ATM)/Fanconi anemia E3 monoubiquitin ligase core complexes (FANC transcripts - A/B/E/F/G/M), FANC2, FANCI, BRCA1, BRCA2, RAD51, PALB2 gene and ATR (ATM- and Rad3-Related) pathway. In conclusion, these findings suggest that a primary target of YM-155 is the loss of replicative DNA repair systems.
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PMID:Effects of Sepantronium Bromide (YM-155) on the Whole Transcriptome of MDA-MB-231 Cells: Highlight on Impaired ATR/ATM Fanconi Anemia DNA Damage Response. 2997 30