Abstract:
:Human lymphoblastoid cells derived from different healthy individuals display considerable variation in their transcription profiles. Here we show that such variation in gene expression underlies interindividual susceptibility to DNA damaging agents. The results demonstrate the massive differences in sensitivity across a diverse cell line panel exposed to an alkylating agent. Computational models identified 48 genes with basal expression that predicts susceptibility with 94% accuracy. Modulating transcript levels for two member genes, MYH and C21ORF56, confirmed that their expression does indeed influence alkylation sensitivity. Many proteins encoded by these genes are interconnected in cellular networks related to human cancer and tumorigenesis.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Fry RC,Svensson JP,Valiathan C,Wang E,Hogan BJ,Bhattacharya S,Bugni JM,Whittaker CA,Samson LDdoi
10.1101/gad.1688508subject
Has Abstractpub_date
2008-10-01 00:00:00pages
2621-6issue
19eissn
0890-9369issn
1549-5477pii
gad.1688508journal_volume
22pub_type
杂志文章abstract::High-fidelity chromosome transmission is fundamental in controlling the quality of the cell division cycle. The spindle pole-to-pole distance remains constant from metaphase to anaphase A. We show that fission yeast sister centromere-connecting proteins, Mis6 and Mis12, are required for correct spindle morphogenesis, ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.13.1664
更新日期:1999-07-01 00:00:00
abstract::C-factor, the product of the csgA gene, is a cell-surface associated short-range intercellular signaling protein in Myxococcus xanthus. C-factor is required for at least four responses during starvation-induced fruiting body morphogenesis: rippling, aggregation, sporulation, and full expression of the csgA gene, all o...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.6.740
更新日期:1996-03-15 00:00:00
abstract::A core promoter element called an initiator (Inr) overlaps the transcription start site of numerous mammalian protein-coding genes. In promoters that lack a TATA box, the Inr is functionally analogous to TATA, in that it is capable of directing basal transcription by RNA polymerase II and of determining the precise si...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.7.821
更新日期:1994-04-01 00:00:00
abstract::The timing of asexual fruiting body formation during Aspergillus nidulans colony development is precisely regulated so that conidiophores are typically produced 1-2 mm behind the growing edge of the colony. Mutations in any of four A. nidulans genes, flbB, flbC, flbD, or flbE, result in colonies that are delayed at le...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.4.491
更新日期:1995-02-15 00:00:00
abstract::Different RNA species are exported from the nucleus by distinct mechanisms. Among the different RNAs, mRNAs and major spliceosomal U snRNAs share several structural similarities, yet they are exported by distinct factors. We previously showed that U1 snRNAs behaved like an mRNA in nuclear export if various approximate...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1216204
更新日期:2004-09-01 00:00:00
abstract::Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a m...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.23.3182
更新日期:1997-12-01 00:00:00
abstract::Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order to study the role of lipid metabolism in myelinating glial cells, we specifically deleted in Schwann cells the Lpin1 gene, which encodes the Mg2+-dependent ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1638008
更新日期:2008-06-15 00:00:00
abstract::The v-erbA oncogene of avian erythroblastosis virus (AEV) encodes a ligand-independent mutated version of the chicken c-erbA alpha-encoded thyroid hormone receptor. The v-erbA gene product, a 75-kD gag/v-erbA fusion protein, is phosphorylated on Ser-16/17 of its v-erbA-encoded domain, and phosphorylation at this site ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.4.10.1663
更新日期:1990-10-01 00:00:00
abstract::The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1224204
更新日期:2004-10-01 00:00:00
abstract::PIWI clade Argonaute proteins silence transposon expression in animal gonads. Their target specificity is defined by bound ∼23- to 30-nucleotide (nt) PIWI-interacting RNAs (piRNAs) that are processed from single-stranded precursor transcripts via two distinct pathways. Primary piRNAs are defined by the endonuclease Zu...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.267252.115
更新日期:2015-08-15 00:00:00
abstract::The association of proteins with the branch site region during pre-mRNA splicing was probed using a novel methodology to site-specifically modify the pre-mRNA with the photo-reagent benzophenone. Three sets of proteins were distinguished by the kinetics of their associations with pre-mRNAs, by their association with d...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.24.3008
更新日期:1994-12-15 00:00:00
abstract::Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo-cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.280941.116
更新日期:2016-05-15 00:00:00
abstract::Telomeres protect the ends of linear chromosomes from degradation and abnormal recombination events, and in vertebrates may be important in cellular senescence and cancer. However, very little is known about the structure of human telomeres. In this report we purify telomeres and analyze their termini. We show that fo...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.21.2801
更新日期:1997-11-01 00:00:00
abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.318675.118
更新日期:2018-12-01 00:00:00
abstract::The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.13.1953
更新日期:1998-07-01 00:00:00
abstract::It is postulated that the symmetric organization of plant lateral organs is based on two crossed axes, the abaxial-adaxial and the lateral axes. The PRESSED FLOWER (PRS) gene, the expression and function of which are dependent on the lateral axis, is reported in this study. In the prs mutant, growth of the lateral sep...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.931001
更新日期:2001-12-15 00:00:00
abstract::Bloom's syndrome (BS) is an autosomal recessive disorder characterized by a strong cancer predisposition. The defining feature of BS is extreme genome instability. The gene mutated in Bloom's syndrome, BLM, encodes a DNA helicase (BLM) of the RecQ family. BLM plays a role in homologous recombination; however, its exac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1609007
更新日期:2007-12-01 00:00:00
abstract::Oncogene-induced senescence (OIS) is a potent tumor suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.286112.116
更新日期:2016-10-01 00:00:00
abstract::Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA was first detected in a subpopulation of myocardial cells at day 8 of embryogenesis. During day 9, abundant hybridization of the ANF probe to the a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.693
更新日期:1987-09-01 00:00:00
abstract::For a number of human genes that encode transcripts containing inverted repeat Alu elements (IRAlus) within their 3' untranslated region (UTR), product mRNA is efficiently exported to the cytoplasm when the IRAlus, which mediate nuclear retention, are removed by alternative polyadenylation. Here we report a new mechan...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.220962.113
更新日期:2013-07-01 00:00:00
abstract::The p53 inhibitor murine double-minute gene 2 (Mdm2) is a target for potential cancer therapies, however increased p53 function can be lethal. To directly address whether reduced Mdm2 function can inhibit tumorigenesis without causing detrimental side effects, we exploited a hypomorphic murine allele of mdm2 to compar...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1378506
更新日期:2006-01-01 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 00:00:00
abstract::The formins constitute a set of protein isoforms encoded by the alternatively spliced transcripts arising from the limb deformity (ld) locus of the mouse. Mutations in this locus disrupt formation of the anteroposterior axis of the embryonic limb. Although ld transcripts are widely expressed during embryogenesis, we h...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.1.29
更新日期:1992-01-01 00:00:00
abstract::We showed previously that the MAP kinase ERK2 is essential for aggregation. erk2 null cells lack cAMP stimulation of adenylyl cyclase and thus cannot relay the cAMP chemotactic signal, although the cells chemotax to cAMP (Segall et al. 1995). In this paper we have examined the role of ERK2 in controlling developmental...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.1.118
更新日期:1996-01-01 00:00:00
abstract::Asymmetric localization of cell fate determinants is a crucial step in neuroblast asymmetric divisions. Whereas several protein kinases have been shown to mediate this process, no protein phosphatase has so far been implicated. In a clonal screen of larval neuroblasts we identified the evolutionarily conserved Protein...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1723609
更新日期:2009-02-01 00:00:00
abstract::The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A gen...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.846800
更新日期:2000-12-01 00:00:00
abstract::Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in Drosophila by a single large cell, the tip cell. It has been postulated that this cell sends out a mitogenic signal that induces the division of neighboring cells. The signal and the molecules that receive it have remained elusive. We show th...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.12.1781
更新日期:1998-06-15 00:00:00
abstract::Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.1120
更新日期:1992-06-01 00:00:00
abstract::RNA polymerase II nascent transcripts are capped during pausing before elongation. Here we report that hSPT5, the human homolog of yeast elongation factor SPT5, interacts directly with the capping enzyme. hSPT5 stimulated capping enzyme guanylylation and mRNA capping by severalfold. Although RNA 5'-triphosphatase acti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.14.1774
更新日期:1999-07-15 00:00:00
abstract::Caenorhabditis elegans GLD-1, a KH motif containing RNA-binding protein of the GSG/STAR subfamily, controls diverse aspects of germ line development, suggesting that it may have multiple mRNA targets. We used an immunoprecipitation/subtractive hybridization/cloning strategy to identify 15 mRNAs that are putative targe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.915901
更新日期:2001-09-15 00:00:00