'Human nuclear DNA topoisomerase I (top1) plays a crucial role in DNA replication, transcription, and chromosome condensation. In this study, we show that intra- and intermolecular guanosine quartets (G-quartets) can inhibit top1-mediated DNA cleavage at a high affinity site. Top1-mediated DNA cleavage was also inhibited by a 16-mer single-stranded oligodeoxynucleotide ... More
The novel WD-repeat protein MORG1 acts as a molecular scaffold for HIF prolyl-hydroxylase 3 (PHD3).
AuthorsHopfer U, Hopfer H, Jablonski K, Stahl RA, Wolf G,
JournalJ Biol Chem
PubMed ID16407229
'Hypoxia-inducible factor-1 (HIF-1), a transcriptional complex composed of an oxygen-sensitive alpha- and a beta-subunit, plays a pivotal role in cellular adaptation to low oxygen availability. Under normoxia, the alpha-subunit of HIF-1 is hydroxylated by a family of prolyl hydroxylases (PHDs) and consequently targeted for proteasomal degradation. Three different prolyl hydroxylases ... More
Coordinated transcription of key pathways in the mouse by the circadian clock.
Authors Panda Satchidananda; Antoch Marina P; Miller Brooke H; Su Andrew I; Schook Andrew B; Straume Marty; Schultz Peter G; Kay Steve A; Takahashi Joseph S; Hogenesch John B;
JournalCell
PubMed ID12015981
'In mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed approximately 650 cycling transcripts and showed that ... More
DEMETER, a DNA glycosylase domain protein, is required for endosperm gene imprinting and seed viability in arabidopsis.
Authors Choi Yeonhee; Gehring Mary; Johnson Lianna; Hannon Mike; Harada John J; Goldberg Robert B; Jacobsen Steven E; Fischer Robert L;
JournalCell
PubMed ID12150995
'We isolated mutations in Arabidopsis to understand how the female gametophyte controls embryo and endosperm development. For the DEMETER (DME) gene, seed viability depends only on the maternal allele. DME encodes a large protein with DNA glycosylase and nuclear localization domains. DME is expressed primarily in the central cell of ... More
The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator.
Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we ... More
Cannabinoids protect astrocytes from ceramide-induced apoptosis through the phosphatidylinositol 3-kinase/protein kinase B pathway.
AuthorsGómez Del Pulgar T, De Ceballos ML, Guzmán M, Velasco G,
JournalJ Biol Chem
PubMed ID12133838
Cannabinoids, the active components of marijuana and their endogenous counterparts, exert many of their actions on the central nervous system by binding to the CB(1) cannabinoid receptor. Different studies have shown that cannabinoids can protect neural cells from different insults. However, those studies have been performed in neurons, whereas no ... More
Different effects on human topoisomerase I by minor groove and intercalated deoxyguanosine adducts derived from two polycyclic aromatic hydrocarbon diol epoxides at or near a normal cleavage site.
Authors Pommier Yves; Kohlhagen Glenda; Laco Gary S; Kroth Heiko; Sayer Jane M; Jerina Donald M;
JournalJ Biol Chem
PubMed ID11832494
Topoisomerase I (top1) relieves supercoiling in DNA by forming transient covalent cleavage complexes. These cleavage complexes can accumulate in the presence of damaged DNA or anticancer drugs that either intercalate or lie in the minor groove. Recently we reported that covalent diol epoxide (DE) adducts of benzo[a]pyrene (BaP) at the ... More
Down-regulation of parkin protein in transient focal cerebral ischemia: A link between stroke and degenerative disease?
Ubiquitylated protein aggregates are characteristic features of neurodegenerative disorders that are also found in acute pathological states of the brain such as stroke. Many of the proteins connected to neurodegenerative diseases play a role in the ubiquitin-proteasomal pathway. Mutation of one of these proteins, the E3 ubiquitin ligase parkin, is ... More
Dose-dependent activation of antiapoptotic and proapoptotic pathways by ethanol treatment in human vascular endothelial cells: differential involvement of adenosine.
Authors Liu Jie; Tian Zhigang; Gao Bin; Kunos George;
JournalJ Biol Chem
PubMed ID11919181
Moderate but not heavy drinking has been found to have a protective effect against cardiovascular morbidity. We investigated the effects of ethanol (EtOH) treatment on the cell survival-promoting phosphatidylinositol 3-kinase (PI3K)/Akt pathway in cultured human umbilical vein endothelial cells (HUVEC). Exposure of cells to 2-20 mm EtOH resulted in rapid ... More