Abstract:
:Cadmium (Cd2+) is a known carcinogen that inactivates the DNA mismatch repair (MMR) pathway. In this study, we have tested the effect of Cd2+ exposure on the enzymatic activity of the mismatch binding complex MSH2-MSH6. Our results indicate that Cd2+ is highly inhibitory to the ATP binding and hydrolysis activities of MSH2-MSH6, and less inhibitory to its DNA mismatch binding activity. The inhibition of the ATPase activity appears to be dose and exposure time dependent. However, the inhibition of the ATPase activity by Cd2+ is prevented by cysteine and histidine, suggesting that these residues are essential for the ATPase activity and are targeted by Cd2+. A comparison of the mechanism of inhibition with N-ethyl maleimide, a sulfhydryl group inhibitor, indicates that this inhibition does not occur through direct inactivation of sulfhydryl groups. Zinc (Zn2+) does not overcome the direct inhibitory effect of Cd2+ on the MSH2-MSH6 ATPase activity in vitro. However, the increase in the mutator phenotype of yeast cells exposed to Cd2+ was prevented by excess Zn2+, probably by blocking the entry of Cd2+ into the cell. We conclude that the inhibition of MMR by Cd2+ is through the inactivation of the ATPase activity of the MSH2-MSH6 heterodimer, resulting in a dominant negative effect and causing a mutator phenotype.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Banerjee S,Flores-Rozas Hdoi
10.1093/nar/gki291keywords:
subject
Has Abstractpub_date
2005-03-03 00:00:00pages
1410-9issue
4eissn
0305-1048issn
1362-4962pii
33/5/1410journal_volume
33pub_type
杂志文章abstract::Guanine-quadruplexes (G4) consist of non-canonical four-stranded helical arrangements of guanine-rich nucleic acid sequences. The bulky and thermodynamically stable features of G4 structures have been shown in many respects to affect normal nucleic acid metabolism. In vivo conversion of G4 structures to single-strande...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr630
更新日期:2011-11-01 00:00:00
abstract::We have shown previously that DNA demethylation by chick embryo 5-methylcytosine (5-MeC)-DNA glycosylase needs both protein and RNA. Amino acid sequences of nine peptides derived from a highly purified 5-MeC-DNA glycosylase complex were identified by Nanoelectrospray ionisation mass spectrometry to be identical to the...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/27.16.3245
更新日期:1999-08-15 00:00:00
abstract::Previous evidence indicates that telomeres resemble common fragile sites and present a challenge for DNA replication. The precise impediments to replication fork progression at telomeric TTAGGG repeats are unknown, but are proposed to include G-quadruplexes (G4) on the G-rich strand. Here we examined DNA synthesis and...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt813
更新日期:2013-12-01 00:00:00
abstract::Enzymatic hydrolysis and base analysis by high performance liquid chromatography showed that mouse satellite DNA had 30-50% less 5-methylcytosine in sperm than in somatic tissue (1.59 mols % vs 2.40-3.11 mols %). Maxam-Gilbert sequencing and analysis of the intensity of the cytosine bands indicated that the level of m...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/13.11.3969
更新日期:1985-06-11 00:00:00
abstract::New transcripts generated by RNA polymerase II (RNAPII) are generally processed in order to form mature mRNAs. Two key processing steps include a precise cleavage within the 3' end of the pre-mRNA, and the subsequent polymerization of adenosines to produce the poly(A) tail. In yeast, these two functions are performed ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx674
更新日期:2017-09-29 00:00:00
abstract::Proper DNA double-strand break (DSB) repair is essential for maintaining genome integrity. Microhomology-mediated end joining (MMEJ) is an error-prone repair mechanism, which introduces mutations at break sites and contributes to chromosomal translocations and telomere fusions, thus driving carcinogenesis. Mitotic kin...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky810
更新日期:2018-11-16 00:00:00
abstract::In synthetic circuits, CRISPR-Cas systems have been used effectively for endpoint changes from an initial state to a final state, such as in logic gates. Here, we use deactivated Cas9 (dCas9) and deactivated Cas12a (dCas12a) to construct dynamic RNA ring oscillators that cycle continuously between states over time in ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa557
更新日期:2020-08-20 00:00:00
abstract::The thumb subdomain, located in various family B DNA polymerases in the C-terminal region, has been shown in their crystal structures to move upon binding of DNA, changing its conformation to nearly completely wrap around the DNA. It has therefore been involved in DNA binding. In agreement with this, partial proteolys...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh184
更新日期:2004-01-16 00:00:00
abstract::Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, t...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw095
更新日期:2016-06-02 00:00:00
abstract::Primer Design Assistant (PDA) is a web interface primer design service combined with thermodynamic theory to evaluate the fitness of primers. It runs in a Linux-Apache-MySQL-PHP structure on a PC equipped with dual CPU (Intel Pentium III 1.4 GHz) and 512 Mb of RAM. A succinct user interface of PDA is accomplished by b...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg560
更新日期:2003-07-01 00:00:00
abstract::We have established a sensitive, monoclonal antibody (Mab)-based procedure permitting the selective enrichment of sequences containing the miscoding alkylation product O6-ethylguanine (O6-EtGua) from mammalian DNA. H5 rat hepatoma cells were reacted with the N-nitroso carcinogen N-ethyl-N-nitrosourea in vitro, to give...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.16.4467
更新日期:1991-08-25 00:00:00
abstract::The effect of temperature and primer concentration on oligonucleotide-primed transcription has been studied using the separated strands of a well-defined natural DNA as template. Results were similar to those obtained in the homopolymer-directed model systems. At high temperature and excess primer concentration mainly...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.2.445
更新日期:1977-02-01 00:00:00
abstract::RegulonDB is a DataBase that integrates biological knowledge of the mechanisms that regulate the transcription initiation in Escherichia coli , as well as knowledge on the organization of the genes and regulatory signals into operons in the chromosome. The operon is the basic structure used in RegulonDB to describe th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.1.55
更新日期:1998-01-01 00:00:00
abstract::The rat beta-casein gene is a member of a small gene family, encoding the principal milk proteins. In order to understand the mechanisms by which its stage- and tissue-specific expression are regulated, initially, a 14 kb genomic clone containing the entire 7.5 kb rat beta-casein gene with 3.5 kb of 5' and 3.0 kb of 3...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.3.1027
更新日期:1988-02-11 00:00:00
abstract::The rabbit homolog to the locus control region (LCR) of the human beta-like globin gene cluster was isolated, and long segments containing the DNase I hypersensitive sites (HS) were sequenced. The order and spacing of HS4, HS3, HS2 and HS1 are conserved between rabbit and human. Alignment of these sequences with their...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.5.1265
更新日期:1993-03-11 00:00:00
abstract::We introduce M-Coffee, a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA. M-Coffee is an extension of T-Coffee and uses consistency to estimate a consensus alignment. We show that the procedure is robust to variations in the choice...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl091
更新日期:2006-03-23 00:00:00
abstract::Despite the increasing wealth of available data, the structure of cancer transcriptional space remains largely unknown. Analysis of this space would provide novel insights into the complexity of cancer, assess relative implications in complex biological processes and responses, evaluate the effectiveness of cancer mod...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr533
更新日期:2011-10-01 00:00:00
abstract::We present a new publicly accessible web-service, RiboSoft, which implements a comprehensive hammerhead ribozyme design procedure. It accepts as input a target sequence (and some design parameters) then generates a set of ranked hammerhead ribozymes, which target the input sequence. This paper describes the implemente...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1111
更新日期:2016-02-29 00:00:00
abstract::Two of the tRNA's found in rabbit reticulocytes are substrates for a post-transcriptional modification leading to the incorporation of guanine into the polynucleotide chain. The major guanylated tRNA was previously identified as tRNA (His). In the present report we show that the minor guanylated tRNA is tRNA (Asn), an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.10.2521
更新日期:1976-10-01 00:00:00
abstract::The pyrrole-imidazole (Py-Im) triamide-cyclopropa pyrroloindole (CPI) conjugates ImPyImLDu86 (7) and ImImPyLDu86 (14) were synthesized and their alkylating activities and inhibitory effects on DNA hydrolysis by restriction endonucleases were examined. Sequencing gel analysis demonstrated that conjugates 7 and 14 speci...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkf486
更新日期:2002-09-01 00:00:00
abstract::DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential mod...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkw183
更新日期:2016-06-20 00:00:00
abstract::High density oligonucleotide array technology is widely used in many areas of biomedical research for quantitative and highly parallel measurements of gene expression. Affymetrix GeneChip arrays are the most popular. In this technology each gene is typically represented by a set of 11-20 pairs of probes. In order to o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gng015
更新日期:2003-02-15 00:00:00
abstract::The Mouse Genome Database (MGD, http://www.informatics.jax.org) is the international community resource for integrated genetic, genomic and biological data about the laboratory mouse. Data in MGD are obtained through loads from major data providers and experimental consortia, electronic submissions from laboratories a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr974
更新日期:2012-01-01 00:00:00
abstract::Affymetrix has recently developed whole-transcript GeneChips-'Gene' and 'Exon' arrays-which interrogate exons along the length of each gene. Although each probe on these arrays is intended to hybridize perfectly to only one transcriptional target, many probes match multiple transcripts located in different parts of th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp853
更新日期:2010-01-01 00:00:00
abstract::Three novel DNA-binding proteins with apparent molecular masses of 7, 10 and 30 kDa have been isolated from the hyperthermophilic methanogen Methanopyrus kandleri. The proteins were identified using a blot overlay assay that was modified to emulate the high ionic strength intracellular environment of M.kandleri protei...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.3.685
更新日期:2002-02-01 00:00:00
abstract::Here we describe a two-stepped photobiotin-based procedure to enrich a target (canine retinal) cDNA library for tissue specific clones without removing those containing repetitive ( SINE ) elements, despite the presence of these elements in the driver population. In a first hybridization excess SINE elements were hybr...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.21.4427
更新日期:1997-11-01 00:00:00
abstract::Two forms of post-transcriptional control direct differential expression of the Saccharomyces cerevisiae genes encoding the AP1-like transcription factors Yap1p and Yap2p. The mRNAs of these genes contain respectively one (YAP1 uORF) and two (YAP2 uORF1 and uORF2) upstream open reading frames. uORF-mediated modulation...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/26.5.1150
更新日期:1998-03-01 00:00:00
abstract::The current version of PLMItRNA has been realized to constitute a database for tRNA molecules and genes identified in the mitochondria of all green plants ( Viridiplantae ). It is the enlargement of a previous database originally restricted to seed plants [Ceci,L.R., Volpicella,M., Liuni,S., Volpetti,V., Licciulli,F. ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.1.159
更新日期:2000-01-01 00:00:00
abstract::A new procedure for the purification of B. subtilis RNA polymerase, based on mild lysis of cells, low speed centrifugation, gel filtration, DEAE-Sephadex chromatography and affinity chromatography on DNA-cellulose, yields three forms of enzyme referred here as enzyme A, B and C. As revealed by SDS gel electrophoresis,...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.3.603
更新日期:1977-03-01 00:00:00
abstract::Loading of the replicative ring helicase onto the origin of replication (oriC) is the final outcome of a well coordinated series of events that collectively constitute a primosomal cascade. Once the ring helicase is loaded, it recruits the primase and signals the switch to the polymerization mode. The transient nature...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh628
更新日期:2004-06-01 00:00:00