Abstract:
:RAG1 and RAG2 catalyze the first DNA cleavage steps in V(D)J recombination. We demonstrate that the isolated central domain of RAG1 has inherent single-stranded (ss) DNA cleavage activity, which does not require, but is enhanced by, RAG2. The central domain, therefore, contains the active-site residues necessary to perform hydrolysis of the DNA phosphodiester backbone. Furthermore, the catalytic activity of this domain on ss DNA is abolished by addition of the C-terminal domain of RAG1. The inhibitory effects of this latter domain are suppressed on substrates containing double-stranded (ds) DNA. Together, the activities of the reconstituted domains on ss versus mixed ds-ss DNA approximate the activity of intact RAG1 in the presence of RAG2. We propose how the combined actions of the RAG1 domains may function in V(D)J recombination and also in aberrant cleavage reactions that may lead to genomic instability in B and T lymphocytes.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
De P,Peak MM,Rodgers KKdoi
10.1128/MCB.24.15.6850-6860.2004subject
Has Abstractpub_date
2004-08-01 00:00:00pages
6850-60issue
15eissn
0270-7306issn
1098-5549pii
24/15/6850journal_volume
24pub_type
杂志文章abstract::Cks proteins associate with cyclin-dependent kinases and have therefore been assumed to play a direct role in cell cycle regulation. Mammals have two paralogs, Cks1 and Cks2, and individually deleting the gene encoding either in the mouse has previously been shown not to impact viability. In this study we show that si...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01833-07
更新日期:2008-09-01 00:00:00
abstract::The retinoblastoma protein (Rb) regulates both the cell cycle and tissue-specific transcription, by modulating the activity of factors that associate with its A-B and C pockets. In skeletal muscle, Rb has been reported to regulate irreversible cell cycle exit and muscle-specific transcription. To identify factors inte...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.23.8903-8915.2000
更新日期:2000-12-01 00:00:00
abstract::The silent mating-type loci of Saccharomyces cerevisiae, HML and HMR, are flanked by transcriptional silencers that have ARS activity (i.e., they function as replication origins when in plasmids). To test whether these ARS elements are chromosomal origins, we mapped origins near HML (close to the left telomere of chro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5346
更新日期:1991-10-01 00:00:00
abstract::The divergently transcribed DIT1 and DIT2 genes of Saccharomyces cerevisiae, which belong to the mid-late class of sporulation-specific genes, are subject to Ssn6-Tup1-mediated repression in mitotic cells. The Ssn6-Tup1 complex, which is required for repression of diverse sets of coordinately regulated genes, is known...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.15.6772-6788.2005
更新日期:2005-08-01 00:00:00
abstract::Integrin signaling plays critical roles in cell adhesion, spreading, and migration, and it is generally accepted that to regulate these integrin functions accurately, localized actin remodeling is required. However, the molecular mechanisms that control the targeting of actin regulation molecules to the proper sites a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00443-10
更新日期:2010-11-01 00:00:00
abstract::The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects telomeres from rapid degradation in Schizosaccharomyces pombe and has been implicated in positive and negative telomere length regulation in humans. Human POT1 appears to interact with telomeres both through direct binding to the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.2.808-818.2005
更新日期:2005-01-01 00:00:00
abstract::Cooperation between STAT3 and c-Jun in driving transcription during transfection of reporter constructs is well established, and both proteins are present on some interleukin-6 (IL-6) STAT3-dependent promoters on chromosomal loci. We report that small interfering RNA knockdown of c-Jun or c-Fos diminishes IL-6 inducti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00613-07
更新日期:2007-09-01 00:00:00
abstract::The Drosophila extra sex combs (esc) protein, a member of the Polycomb group (PcG), is a transcriptional repressor of homeotic genes. Genetic studies have shown that esc protein is required in early embryos at about the time that other PcG proteins become engaged in homeotic gene repression. The esc protein consists p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.11.6663
更新日期:1997-11-01 00:00:00
abstract::The first intron of the human collagen alpha 1(I) gene contains several positively and negatively acting elements. We have studied the transcription of collagen-human growth hormone fusion genes, containing deletions and rearrangements of collagen intronic sequences, by transient transfection of chick tendon fibroblas...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.11.4851
更新日期:1988-11-01 00:00:00
abstract::Recombination and synapsis of homologous chromosomes are hallmarks of meiosis in many organisms. Meiotic recombination is initiated by Spo11-induced DNA double-strand breaks (DSBs), whereas chromosome synapsis is mediated by a tripartite structure named the synaptonemal complex (SC). Previously, we proposed that buddi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00438-13
更新日期:2013-08-01 00:00:00
abstract::The heterochromatic domains of Drosophila melanogaster (pericentric heterochromatin, telomeres, and the fourth chromosome) are characterized by histone hypoacetylation, high levels of histone H3 methylated on lysine 9 (H3-mK9), and association with heterochromatin protein 1 (HP1). While the specific interaction of HP1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.18.8210-8220.2004
更新日期:2004-09-01 00:00:00
abstract::The yeast nuclear gene YME1 was one of six genes recently identified in a screen for mutations that elevate the rate at which DNA escapes from mitochondria and migrates to the nucleus. yme1 mutations, including a deletion, cause four known recessive phenotypes: an elevation in the rate at which copies of TRP1 and ARS1...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.9.5418
更新日期:1993-09-01 00:00:00
abstract::Cytochrome P450 oxidoreductase (POR) is the obligate electron donor for all microsomal cytochrome P450 enzymes, which catalyze the metabolism of a wide spectrum of xenobiotic and endobiotic compounds. Point mutations in POR have been found recently in patients with Antley-Bixler-like syndrome, which includes limb skel...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01638-08
更新日期:2009-05-01 00:00:00
abstract::Distal intraexon (iE) regulatory elements in 4.1R pre-mRNA govern 3' splice site choice at exon 2 (E2) via nested splicing events, ultimately modulating expression of N-terminal isoforms of cytoskeletal 4.1R protein. Here we explored intrasplicing in other normal and disease gene contexts and found conservation of int...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05716-11
更新日期:2012-06-01 00:00:00
abstract::In the acellular slime mold Physarum polycephalum, the several hundred genes coding for rRNA are located on linear extrachromosomal DNA molecules of a discrete size, 60 kilobases. Each molecule contains two genes that are arranged in a palindromic fashion and separated by a central spacer region. We investigated how r...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.3.4.635
更新日期:1983-04-01 00:00:00
abstract::The tyrosine kinase activity of the epidermal growth factor (EGF) receptor is regulated by a truncated receptor of 100 kilodaltons (kDa) that contains the EGF-binding site but not the kinase domain. The inhibition of kinase is not due to competition for available EGF or for the kinase substrate-binding site. Chemical ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.2.671
更新日期:1989-02-01 00:00:00
abstract::We identified and partially purified a phosphatase from crude extracts of Saccharomyces cerevisiae cells that can catalyze the last step of tRNA splicing in vitro. This phosphatase can remove the 2'-phosphate left over at the splice junction after endonuclease has removed the intron and ligase has joined together the ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.3.1049
更新日期:1990-03-01 00:00:00
abstract::A single-base deletion within the protein-coding region of the adenovirus type 5 early region 1A (E1A) genes, 399 bases downstream from the transcription start site, depresses transcription to 2% of the wild-type rate. Complementation studies demonstrated that this was due to two effects of the mutation: first, inacti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.7.1293
更新日期:1984-07-01 00:00:00
abstract::Expression of the anaphase-promoting complex/cyclosome (APC/C) inhibitor Emi1 is required for the accumulation of APC/C substrates crucial for DNA synthesis and mitotic entry. We show that in vivo Emi1 expression correlates with the proliferative status of the cellular compartment and that cells lacking Emi1 undergo c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00908-07
更新日期:2007-11-01 00:00:00
abstract::The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an approximately 72-kDa tyrosine-phosphorylated protein, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.6.2227-2241.2005
更新日期:2005-03-01 00:00:00
abstract::We provide evidence that the human DNA ligase III gene encodes a mitochondrial form of this enzyme. First, the DNA ligase III cDNA contains an in-frame ATG located upstream from the putative translation initiation start site. The DNA sequence between these two ATG sites encodes an amphipathic helix similar to previous...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.5.3869
更新日期:1999-05-01 00:00:00
abstract::Multiple members of the A, B, and C clusters of Hox genes are expressed in hematopoietic cells. Several of these Hox genes have been found to display distinctive expression patterns, with genes located at the 3' side of the clusters being expressed at their highest levels in the most primitive subpopulation of human C...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.1.495
更新日期:1997-01-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds telomeric sequence repeats to the ends of linear chromosomes. In vitro, telomerase has been observed to add repeats to a DNA oligonucleotide primer in a processive manner, leading to the postulation of a DNA anchor site separate from the catalytic site of the enzyme. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.1.296
更新日期:1997-01-01 00:00:00
abstract::Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37 degrees C for filamen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.13.4635-4647.2000
更新日期:2000-07-01 00:00:00
abstract::The small subunit of ribonucleotide reductase in Saccharomyces cerevisiae (RNR2) was induced 3- to 20-fold by a variety of DNA-damaging agents. Induction of the RNR2 transcript by at least one of these agents, methyl methanesulfonate, did not require protein synthesis. To identify sequences involved in the regulation ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.12.5359
更新日期:1989-12-01 00:00:00
abstract::TEL-JAK2 fusion proteins, which are a result of t(9;12)(p24;p13) translocations associated with human leukemia, activate Stat5 in vitro and in vivo and cause a myelo- and lymphoproliferative disease in a murine bone marrow transplant model. We report that Socs-1, a member of the SOCS family of endogenous inhibitors of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.10.3547-3557.2001
更新日期:2001-05-01 00:00:00
abstract::Repetitive DNA sequences have been implicated in the mediation of DNA rearrangement in mammalian cells. We have tested this hypothesis by using a dihydrofolate reductase (DHFR) expression vector into which candidate sequences were inserted. DHFR- Chinese hamster ovary (CHO) cells were transfected with this vector, the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.9.3611
更新日期:1988-09-01 00:00:00
abstract::Monoclonal antibodies to fibrillin 1 (MP340), a component of elastin-associated microfibrils, were used to screen cDNA libraries made from bovine nuchal ligament mRNA. One of the selected clones (cL9; 1.2 kb) hybridized on Northern (RNA) blotting with nuchal ligament mRNA to two abundant mRNAs of 9.0 and 7.5 kb, which...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.12.6932
更新日期:1995-12-01 00:00:00
abstract::We have isolated new histone H3 mutants in Saccharomyces cerevisiae that confer phenotypes indicative of transcriptional defects. Here we describe the characterization of one such mutant, encoded by the hht2-11 allele, which contains the single amino acid change L61W in the globular domain of H3. Whole-genome expressi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.2.561-572.2004
更新日期:2004-01-01 00:00:00
abstract::Eukaryotic flagella are complex organelles composed of more than 200 polypeptides. Little is known about the regulatory mechanisms governing synthesis of the flagellar protein subunits and their assembly into this complex organelle. The unicellular green alga Chlamydomonas reinhardtii is the premier experimental model...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.7.3858
更新日期:1997-07-01 00:00:00