Abstract:
:Flap endonuclease-1 (FEN1) is a member of the Rad2 structure-specific nuclease family. FEN1 possesses FEN, 5'-exonuclease and gap-endonuclease activities. The multiple nuclease activities of FEN1 allow it to participate in numerous DNA metabolic pathways, including Okazaki fragment maturation, stalled replication fork rescue, telomere maintenance, long-patch base excision repair and apoptotic DNA fragmentation. Here, we summarize the distinct roles of the different nuclease activities of FEN1 in these pathways. Recent biochemical and genetic studies indicate that FEN1 interacts with more than 30 proteins and undergoes post-translational modifications. We discuss how FEN1 is regulated via these mechanisms. Moreover, FEN1 interacts with five distinct groups of DNA metabolic proteins, allowing the nuclease to be recruited to a specific DNA metabolic complex, such as the DNA replication machinery for RNA primer removal or the DNA degradosome for apoptotic DNA fragmentation. Some FEN1 interaction partners also stimulate FEN1 nuclease activities to further ensure efficient action in processing of different DNA structures. Post-translational modifications, on the other hand, may be critical to regulate protein-protein interactions and cellular localizations of FEN1. Lastly, we also review the biological significance of FEN1 as a tumor suppressor, with an emphasis on studies of human mutations and mouse models.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Zheng L,Jia J,Finger LD,Guo Z,Zer C,Shen Bdoi
10.1093/nar/gkq884subject
Has Abstractpub_date
2011-02-01 00:00:00pages
781-94issue
3eissn
0305-1048issn
1362-4962pii
gkq884journal_volume
39pub_type
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journal_title:Nucleic acids research
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abstract::Therapeutic small interfering RNAs (siRNAs) are composed of chemically modified nucleotides, which enhance RNA stability and increase affinity in Watson-Crick base pairing. However, the precise fate of such modified nucleotides once the siRNA is degraded within the cell is unknown. Previously, we demonstrated that deo...
journal_title:Nucleic acids research
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abstract::The Mouse Genome Database (MGD) (http://www.informatics.jax.org) is the community model organism database resource for the laboratory mouse, a premier animal model for the study of genetic and genomic systems relevant to human biology and disease. MGD maintains a comprehensive catalog of genes, functional RNAs and oth...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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doi:10.1093/nar/12.15.6031
更新日期:1984-08-10 00:00:00
abstract::Site-directed RNA editing (SDRE) is a strategy to precisely alter genetic information within mRNAs. By linking the catalytic domain of the RNA editing enzyme ADAR to an antisense guide RNA, specific adenosines can be converted to inosines, biological mimics for guanosine. Previously, we showed that a genetically encod...
journal_title:Nucleic acids research
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abstract::The synthetic DNA fragment (formula, see text) (corresponding to nucleotides 4299-4314 of the phi X DNA sequence) was cloned into either the AmpR gene or the KmR gene of plasmid pACYC 177. The DNA sequence of the KmR gene around the insertion site was determined by nucleotide sequence analysis of the pACYC 177 FnudII ...
journal_title:Nucleic acids research
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abstract::EcoGene (http://ecogene.org) is a database and website devoted to continuously improving the structural and functional annotation of Escherichia coli K-12, one of the most well understood model organisms, represented by the MG1655(Seq) genome sequence and annotations. Major improvements to EcoGene in the past decade i...
journal_title:Nucleic acids research
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更新日期:2013-01-01 00:00:00
abstract::Discovering which regulatory proteins, especially transcription factors (TFs), are active under certain experimental conditions and identifying the corresponding binding motifs is essential for understanding the regulatory circuits that control cellular programs. The experimental methods used for this purpose are labo...
journal_title:Nucleic acids research
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doi:10.1093/nar/gkp554
更新日期:2009-09-01 00:00:00
abstract::The cis-requirements for the first editing site in the atp9 mRNA from pea mitochondria were investigated in an in vitro RNA editing system. Template RNAs deleted 5' of -20 are edited correctly, but with decreased efficiency. Deletions between -20 and the edited nucleotide abolish editing activity. Substitution of the ...
journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
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doi:10.1093/nar/26.7.1689
更新日期:1998-04-01 00:00:00
abstract::Different helical conformations of DNA (D), RNA (R), and DNA.RNA (DR) hybrid double and triple helices have been detected using affinity cleavage analysis. Synthetic methods were developed to attach EDTA.Fe to a single nucleotide on RNA as well as DNA oligonucleotides. Cleavage patterns generated by a localized diffus...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.14.2837
更新日期:1994-07-25 00:00:00
abstract::The promoter of the human BCR gene, regulating the transcription of the chimeric BCR/ABL mRNA in leukemia, has been isolated and characterized. A region of 1.1 kb immediately 5' to the transcription start site was analyzed in detail by sequencing, DNase 1 footprinting, gel retardation and functional studies. These exp...
journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1990-12-11 00:00:00
abstract::Escherichia coli Exonuclease I (ExoI) digests single-stranded DNA (ssDNA) in the 3'-5' direction in a highly processive manner. The crystal structure of ExoI, determined previously in the absence of DNA, revealed a C-shaped molecule with three domains that form a central positively charged groove. The active site is a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt278
更新日期:2013-06-01 00:00:00
abstract::We describe an improved model of DNA replication in Xenopus egg extracts, in which a circular plasmid immobilized on paramagnetic beads is used as a template. DNA synthesis occurred on either circular or linear plasmids coupled to the beads, but only DNA synthesis on the circular plasmid was inhibited by geminin and a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl512
更新日期:2006-07-26 00:00:00
abstract::An updated compilation of 300 E. coli mRNA promoter sequences is presented. For each sequence the most recent relevant paper was checked, to verify the location of the transcriptional start position as identified experimentally. We comment on the reliability of the sequence databanks and analyze the conservation of kn...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.7.1507
更新日期:1993-04-11 00:00:00
abstract::We have microinjected genomic DNA clones containing the Moloney murine leukemia virus (M-MuLV) proviral genome and flanking mouse sequences from Mov-3, Mov-7 and Mov-10 mice into Xenopus laevis oocytes and analyzed the virus-specific transcription and translation products. These mouse strains carry a proviral genome c...
journal_title:Nucleic acids research
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doi:10.1093/nar/11.12.3989
更新日期:1983-06-25 00:00:00
abstract::We have investigated the response of the filamentous fungus Aspergillus nidulans to low, non-killing, doses of the alkylating agent MNNG (N-methyl-N'-nitro-N-nitrosoguanidine). Such treatment causes a substantial induction of DNA alkyltransferase activity, with the specific activity in treated cells increasing up to o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.4.645
更新日期:1992-02-25 00:00:00
abstract::Gene set enrichment testing can enhance the biological interpretation of ChIP-seq data. Here, we develop a method, ChIP-Enrich, for this analysis which empirically adjusts for gene locus length (the length of the gene body and its surrounding non-coding sequence). Adjustment for gene locus length is necessary because ...
journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2014-07-01 00:00:00
abstract::The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases (https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz943
更新日期:2020-01-08 00:00:00
abstract::Neph et al. (2012) (Circuitry and dynamics of human transcription factor regulatory networks. Cell, 150: 1274-1286) reported the transcription factor (TF) regulatory networks of 41 human cell types using the DNaseI footprinting technique. This provides a valuable resource for uncovering regulation principles in differ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku923
更新日期:2014-11-10 00:00:00
abstract::The hexametric T7 helicase (gp4) adopts a spiral lock-washer form and encircles a coil-like DNA (tracking) strand with two nucleotides bound to each subunit. However, the chemo-mechanical coupling mechanism in unwinding has yet to be elucidated. Here, we utilized nanotensioner-enhanced Förster resonance energy transfe...
journal_title:Nucleic acids research
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更新日期:2020-04-06 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.23.4914
更新日期:1994-11-25 00:00:00
abstract::We have isolated from a single human liver cDNA library two clones which are highly homologous (78% over the coding region) to the major phenobarbital-inducible P450 from rat (P450IIB1). This is the first direct demonstration of the presence of the P450IIB gene subfamily in humans. This subfamily is much less extensiv...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.13.5783
更新日期:1988-07-11 00:00:00
abstract::Methionyl-tRNA synthetase belongs to the class I aminoacyl-tRNA synthetase family characterized both by a catalytic center built around a Rossmann Fold and by the presence of the two peptidic marker sequences HIGH and KMSKS. In this study, the role of the 21HLGH24 motif of Escherichia coli methionyl-tRNA synthetase wa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.23.4793
更新日期:1995-12-11 00:00:00
abstract::GC-AG introns represent 0.7% of total human pre-mRNA introns. To study the function of GC-AG introns in splicing regulation, 196 cDNA-confirmed GC-AG introns were identified in Caenorhabditis elegans. These represent 0.6% of the cDNA- confirmed intron data set for this organism. Eleven of these GC-AG introns are invol...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkf465
更新日期:2002-08-01 00:00:00
abstract::The estrogen receptor (ER) contains two nonacidic transcriptional activation functions, AF-1 and AF-2 (formerly TAF-1 and TAF-2). In this study we show that AF-1 and AF-2 are able to stimulate transcription in vitro in a HeLa cell system when fused to the DNA binding domain of the yeast activator GAL4. We also demonst...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.1.5
更新日期:1993-01-11 00:00:00
abstract::Bacteria from the genus Streptomyces are very important for the production of natural bioactive compounds such as antibiotic, antitumour or immunosuppressant drugs. Around two-thirds of all known natural antibiotics are produced by these bacteria. An enormous quantity of crucial data related to this genus has been gen...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1253
更新日期:2013-01-01 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::Preparation of the two nonanucleotides, d(pG-G-A-G-G-A-G-A-A) and d(pT-T-C-T-G-T-T-G-A), and the octanucleotide, d(pT-G-G-C-C-C-A-T) is described by a rapid solid-phase method on a polyamide support. The syntheses were carried out using a modified solid-phase peptide synthesiser and required one day for each nucleotid...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/4.12.4391
更新日期:1977-12-01 00:00:00
abstract::siRNAs confer sequence specific and robust silencing of mRNA. By virtue of these properties, siRNAs have become therapeutic candidates for disease intervention. However, their use as therapeutic agents can be hampered by unintended off-target effects by either or both strands of the siRNA duplex. We report here that u...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq961
更新日期:2011-03-01 00:00:00