BMC Molecular Biology最新文献

{"title":"Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells","authors":"Yuan Lu,&nbsp;Jilong Li,&nbsp;Jianlin Cheng,&nbsp;Dennis B. Lubahn","doi":"10.1186/s12867-015-0049-1","DOIUrl":"https://doi.org/10.1186/s12867-015-0049-1","url":null,"abstract":"<p>Orphan nuclear receptor estrogen related receptor β (Esrrb or ERRβ) is well known in stem cells and early embryonic development. However, little is known about its function in cancer.</p><p>We investigated the mRNA profile alterations induced by Esrrb expression and its synthetic ligand DY131 in human prostate cancer DU145 cells via RNA-Seq analysis.</p><p>We distinguished 67 mRNAs differentially expressed by Esrrb alone. Although DY131 alone did not change any gene, treatment of DY131 in the presence of Esrrb altered 1161 mRNAs. These observations indicated Esrrb had both ligand-independent and ligand-dependent activity. When Esrrb was expressed, DY131 treatment further regulated 15 Esrrb-altered mRNAs. DY131 acted as an antagonist for 11 of 15 mRNAs (<i>wdr52</i>, <i>f13a1</i>, <i>pxdn</i>, <i>spns2</i>, <i>loc100506599</i>, <i>tagln</i>, <i>loc441454</i>, <i>tkel1</i>, <i>sema3f</i>, <i>zcwpw2</i>, <i>sdc2</i>) and as an agonist for 4 of the 15 mRNAs (<i>rarres3</i>, <i>oasl</i>, <i>padi2</i>, <i>ddx60</i>). Gene ontology analyses showed altered genes are related to transcription and translation regulation, cell proliferation and apoptosis regulation, and cellular metabolism.</p><p>Our results characterized mRNA profiles in DU145 prostate cancer cells driven by Esrrb expression and Esrrb ligand DY131, and provided multiple markers to characterize Esrrb’s function in Esrrb research.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0049-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4013444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature-induced variation in gene expression burst size in metazoan cells","authors":"Ophélie Arnaud,&nbsp;Sam Meyer,&nbsp;Elodie Vallin,&nbsp;Guillaume Beslon,&nbsp;Olivier Gandrillon","doi":"10.1186/s12867-015-0048-2","DOIUrl":"https://doi.org/10.1186/s12867-015-0048-2","url":null,"abstract":"<p>Gene expression is an inherently stochastic process, owing to its dynamic molecular nature. Protein amount distributions, which can be acquired by cytometry using a reporter gene, can inform about the mechanisms of the underlying microscopic molecular system.</p><p>By using different clones of chicken erythroid progenitor cells harboring different integration sites of a CMV-driven mCherry protein, we investigated the dynamical behavior of such distributions. We show that, on short term, clone distributions can be quickly regenerated from small population samples with a high accuracy. On longer term, on the contrary, we show variations manifested by correlated fluctuation in the Mean Fluorescence Intensity. In search for a possible cause of this correlation, we demonstrate that in response to small temperature variations cells are able to adjust their gene expression rate: a modest (2?°C) increase in external temperature induces a significant down regulation of mean expression values, with a reverse effect observed when the temperature is decreased. Using a two-state model of gene expression we further demonstrate that temperature acts by modifying the size of transcription bursts, while the burst frequency of the investigated promoter is less systematically affected.</p><p>For the first time, we report that transcription burst size is a key parameter for gene expression that metazoan cells from homeotherm animals can modify in response to an external thermal stimulus.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0048-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4984758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genes targeted by the Hedgehog-signaling pathway can be regulated by Estrogen related receptor β","authors":"Yuan Lu,&nbsp;Jilong Li,&nbsp;Jianlin Cheng,&nbsp;Dennis B. Lubahn","doi":"10.1186/s12867-015-0047-3","DOIUrl":"https://doi.org/10.1186/s12867-015-0047-3","url":null,"abstract":"<p>Nuclear receptor family member, Estrogen related receptor β, and the Hedgehog signal transduction pathway are both reported to relate to tumorigenesis and induced pluripotent stem cell reprogramming. We hypothesize that Estrogen related receptor β can modulate the Hedgehog signaling pathway and affect Hedgehog driven downstream gene expression.</p><p>We established an estrogen related receptor β-expressing Hedgehog-responsive NIH3T3 cell line by Esrrb transfection, and performed mRNA profiling using RNA-Seq after Hedgehog ligand conditioned medium treatment. Esrrb expression altered 171 genes, while Hedgehog signaling activation alone altered 339 genes. Additionally, estrogen related receptor β expression in combination with Hedgehog signaling activation affects a group of 109 Hedgehog responsive mRNAs, including <i>Hsd11b1</i>, <i>Ogn</i>, <i>Smoc2</i>, <i>Igf1, Pdcd4, Igfbp4, Stmn1, Hp, Hoxd8, Top2a, Tubb4b, Sfrp2, Saa3, Prl2c3</i> and <i>Dpt</i>.</p><p>We conclude that Estrogen related receptor β is capable of interacting with Hh-signaling downstream targets. Our results suggest a new level of regulation of Hedgehog signaling by Estrogen related receptor β, and indicate modulation of Estrogen related receptor β can be a new strategy to regulate various functions driven by the Hedgehog signaling pathway.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0047-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4906379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA double-strand break repair is impaired in presenescent Syrian hamster fibroblasts","authors":"Ljudmila Solovjeva,&nbsp;Denis Firsanov,&nbsp;Anastasia Vasilishina,&nbsp;Vadim Chagin,&nbsp;Nadezhda Pleskach,&nbsp;Andrey Kropotov,&nbsp;Maria Svetlova","doi":"10.1186/s12867-015-0046-4","DOIUrl":"https://doi.org/10.1186/s12867-015-0046-4","url":null,"abstract":"<p>Studies of DNA damage response are critical for the comprehensive understanding of age-related changes in cells, tissues and organisms. Syrian hamster cells halt proliferation and become presenescent after several passages in standard conditions of cultivation due to what is known as??culture stress?. Using proliferating young and non-dividing presenescent cells in primary cultures of Syrian hamster fibroblasts, we defined their response to the action of radiomimetic drug bleomycin (BL) that induces DNA double-strand breaks (DSBs).</p><p>The effect of the drug was estimated by immunoblotting and immunofluorescence microscopy using the antibody to phosphorylated histone H2AX (gH2AX), which is generally accepted as a DSB marker. At all stages of the cell cycle, both presenescent and young cells demonstrated variability of the number of gH2AX foci per nucleus. gH2AX focus induction was found to be independent from BL-hydrolase expression. Some differences in DSB repair process between BL-treated young and presenescent Syrian hamster cells were observed: (1) the kinetics of gH2AX focus loss in G0 fibroblasts of young culture was faster than in cells that prematurely stopped dividing; (2) presenescent cells were characterized by a slower recruitment of DSB repair proteins 53BP1, phospho-DNA-PK and phospho-ATM to gH2AX focal sites, while the rate of phosphorylated ATM/ATR substrate accumulation was the same as that in young cells.</p><p>Our results demonstrate an impairment of DSB repair in prematurely aged Syrian hamster fibroblasts in comparison with young fibroblasts, suggesting age-related differences in response to BL therapy.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0046-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4508561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering targeting rules of splicing modulator compounds: case of TG003","authors":"Maki Sakuma,&nbsp;Kei Iida,&nbsp;Masatoshi Hagiwara","doi":"10.1186/s12867-015-0044-6","DOIUrl":"https://doi.org/10.1186/s12867-015-0044-6","url":null,"abstract":"<p>Recent advances in the development of small chemical compounds that can modulate RNA splicing brought excitement to the field of splicing-targeting therapy. Splicing-targeting therapy tries to ameliorate the disease by altering the exon combination of transcripts to reduce the undesired effect of genetic mutations. However, the knowledge and tools to understand factors contributing to splicing modulator compound sensitivity have been lacking. Our goal was to establish a method to characterize sequence features found in compound sensitive exons.</p><p>Here we developed a comparative transcriptomic approach to explore features that make an exon sensitive to a chemical compound. In this study, we chose TG003, a potential drug for <i>Duchenne</i> muscular dystrophy, and performed RNA-sequencing on samples from human and mouse skeletal muscle cells, with and without TG003 treatments. We compared TG003 responsiveness between homologous exon pairs and identified 21 pairs in which human exons were skip-enhanced but not mouse exons. We compared the sequence features; splice site scores, number of splicing factor binding sites, and properties of branch sequence and polypyrimidine tracts, and found that polypyrimidine tracts were stronger (longer stretches and richer content of consecutive polypyrimidine) in the mouse TG003 insensitive exons. We also compared the features between TG003 skip-enhanced and insensitive exons within the species, and discovered that human TG003 skip-enhanced exons were shorter and had less splicing factor binding sites than the group of human TG003 insensitive exons. Mouse insensitive exons homologous to human TG003 skip-enhanced exons shared these properties. Our results suggested that these features are prerequisites for TG003 skip-enhanced exons and weak polypyrimidine tracts are defining features, which were supported by a decision tree analysis on all cassette exons in human.</p><p>In this study we established a comparative transcriptomic approach, which shed lights on how small chemical compounds modulate RNA splicing. The results described here was the first attempt to decipher the targeting rules of a splicing modulator compound. We expect that this approach would contribute to the precise understanding of the mechanism of TG003-induced splicing modulation, expand target diseases of splicing modulators in general, as well as the development of new splicing modulators.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0044-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4951507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The elongation factor eEF3 (Yef3) interacts with mRNA in a translation independent manner","authors":"Nitzan Samra,&nbsp;Avigail Atir-Lande,&nbsp;Lilach Pnueli,&nbsp;Yoav Arava","doi":"10.1186/s12867-015-0045-5","DOIUrl":"https://doi.org/10.1186/s12867-015-0045-5","url":null,"abstract":"<p>mRNA binding proteins (RBPs) constitute 10–15?% of the eukaryotic proteome and play important part in post-transcriptional regulation of gene expression. Due to the instability of RNA and the transient nature its interaction with RBPs, identification of novel RBPs is a significant challenge. Recently, a novel methodology for RBP purification and identification (termed RaPID) was presented, which allows high affinity purification of RBPs while associated with mRNA in vivo.</p><p>We performed a RaPID screen for proteins that interact with PMP1 mRNA in order to identify novel mRNA binding proteins. PMP1 mRNA was tagged in its 3′ UTR with multiple MS2 loops and co-expressed with MS2-binding protein fused to streptavidin binding protein (SBP). RNA–protein complexes were cross-linked in vivo and isolated through streptavidin beads. The eluted proteins were subjected to mass spectroscopy analysis. The screen identified many proteins, about half of them were previously shown to bind RNA. We focused on eEF3 (YEF3), an essential translation elongation factor that interacts with ribosomes. Purification of TAP-tagged Yef3 with its associated RNAs confirmed that the native PMP1 transcript is associated with it. Intriguingly, high association with Yef3-TAP was observed when purification was performed in the presence of EDTA, and with PMP1 that contains stop codons immediately downstream to the initiation codon. Furthermore, high association was observed with a transcript containing only the 3′ UTR of PMP1. Complementary, RaPID isolation of MS2-tagged 3′ UTRs with their associated proteins revealed that Yef3 can efficiently interact with these regions.</p><p>This study identifies many novel proteins that interact with PMP1 mRNA. Importantly, the elongation factor Yef3 was found to interact with mRNA in non-coding regions and in a translation independent manner. These results suggest an additional, non-elongation function for this factor.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0045-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4957164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RE1 silencing transcription factor (REST) negatively regulates ALL1-fused from chromosome 1q (AF1q) gene transcription","authors":"Yuanyuan Hu,&nbsp;Qianwen Sun,&nbsp;Chen Zhang,&nbsp;Qingquan Sha,&nbsp;Xiulian Sun","doi":"10.1186/s12867-015-0043-7","DOIUrl":"https://doi.org/10.1186/s12867-015-0043-7","url":null,"abstract":"<p>ALL1-fused from chromosome 1q (AF1q), originally considered as an oncogenic factor, has been implicated in neuronal development; however, its upstream regulatory mechanisms in neural system remained elusive.</p><p>Our study showed that REST (RE1 silencing transcription factor), a key transcription factor in neurodevelopment, could down-regulate the gene expression of <i>AF1q</i>. The promoter assay identified a neuron-restrictive silencer element at ?383 to ?363?bp of human <i>AF1q</i> promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (CHIP) confirmed the binding of REST to the NRSE in <i>AF1q</i> gene promoter. Additionally, the negative correlation between the expression levels of <i>Af1q</i> and <i>Rest</i> in mice neurodevelopment supported the negative regulation of <i>AF1q</i> by REST and the potential functions of AF1q in neurodevelopment.</p><p>These results demonstrate that REST regulates <i>AF1q</i> gene transcription through directly binding to a NRSE at ?383 to ?363?bp of <i>AF1q</i> promoter.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0043-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4231466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM28 as a novel transcriptional elongation factor","authors":"Heeyoun Bunch,&nbsp;Stuart K Calderwood","doi":"10.1186/s12867-015-0040-x","DOIUrl":"https://doi.org/10.1186/s12867-015-0040-x","url":null,"abstract":"<p>TRIM28 is a multidomain protein with versatile functions in transcription and DNA repair. Recently it was shown that this factor plays unanticipated roles in transcriptional elongation. TRIM28 was shown to stabilize the pausing of RNA polymerase II (Pol II) close to the transcriptional start site in many unactivated genes, permitting Pol II accumulation and readying genes for induction. In addition, the factor was shown to respond rapidly to signals accompanying transcriptional activation permitting the productive elongation of RNA by previously paused Pol II. We discuss here critical regulatory mechanisms of TRIM28 in transcriptional control and DNA repair that may illuminate the novel roles of this factor in pausing and elongation of Pol II.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0040-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4811873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis artefacts of the INS-IGF2 fusion transcript","authors":"Rasmus Wernersson,&nbsp;Thomas Frogne,&nbsp;Claude Rescan,&nbsp;Lena Hansson,&nbsp;Christine Bruun,&nbsp;Mads Grønborg,&nbsp;Jan Nygaard Jensen,&nbsp;Ole Dragsbæk Madsen","doi":"10.1186/s12867-015-0042-8","DOIUrl":"https://doi.org/10.1186/s12867-015-0042-8","url":null,"abstract":"<p>In gene expression analysis, overlapping genes, splice variants, and fusion transcripts are potential sources of data analysis artefacts, depending on how the observed intensity is assigned to one, or more genes. We here exemplify this by an in-depth analysis of the INS-IGF2 fusion transcript, which has recently been reported to be among the highest expressed transcripts in human pancreatic beta cells and its protein indicated as a novel autoantigen in Type 1 Diabetes.</p><p>Through RNA sequencing and variant specific qPCR analyses we demonstrate that the true abundance of INS-IGF2 is &gt;20,000 fold lower than INS in human beta cells, and we suggest an explanation to the nature of the artefacts which have previously led to overestimation of the gene expression level in selected studies. We reinvestigated the previous reported findings of detection of INS-IGF2 using antibodies both in Western blotting and immunohistochemistry. We found that the one available commercial antibody (BO1P) raised against recombinant INS-IGF2 show strong cross-reaction to native proinsulin, and we did not detect INS-IGF2 protein in the human beta cell line EndoC-βH1. Furthermore, using highly sensitive proteomics analysis we could not demonstrate INS-IGF2 protein in samples of human islets nor in EndoC-βH1.</p><p>Sequence features, such as fusion transcripts spanning multiple genes can lead to unexpected results in gene expression analysis, and care must be taken in generating and interpreting the results. For the specific case of INS-IGF2 we conclude that the abundance of the fusion transcript/protein is exceedingly lower than previously reported, and that current immuno-reagents available for detecting INS-IGF2 protein have a strong cross-reaction to native human proinsulin. Finally, we were unable to detect INS-IGF2 protein by proteomics analysis.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0042-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5114182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9–Rad1–Hus1 checkpoint clamp","authors":"Bor-Jang Hwang,&nbsp;Jin Jin,&nbsp;Ying Gao,&nbsp;Guoli Shi,&nbsp;Amrita Madabushi,&nbsp;Austin Yan,&nbsp;Xin Guan,&nbsp;Michal Zalzman,&nbsp;Satoshi Nakajima,&nbsp;Li Lan,&nbsp;A-Lien Lu","doi":"10.1186/s12867-015-0041-9","DOIUrl":"https://doi.org/10.1186/s12867-015-0041-9","url":null,"abstract":"<p>SIRT6, a member of the NAD⁺-dependent histone/protein deacetylase family, regulates genomic stability, metabolism, and lifespan. MYH glycosylase and APE1 are two base excision repair (BER) enzymes involved in mutation avoidance from oxidative DNA damage. Rad9–Rad1–Hus1 (9–1–1) checkpoint clamp promotes cell cycle checkpoint signaling and DNA repair. BER is coordinated with the checkpoint machinery and requires chromatin remodeling for efficient repair. SIRT6 is involved in DNA double-strand break repair and has been implicated in BER. Here we investigate the direct physical and functional interactions between SIRT6 and BER enzymes.</p><p>We show that SIRT6 interacts with and stimulates MYH glycosylase and APE1. In addition, SIRT6 interacts with the 9-1-1 checkpoint clamp. These interactions are enhanced following oxidative stress. The interdomain connector of MYH is important for interactions with SIRT6, APE1, and 9–1–1. Mutagenesis studies indicate that SIRT6, APE1, and Hus1 bind overlapping but different sequence motifs on MYH. However, there is no competition of APE1, Hus1, or SIRT6 binding to MYH. Rather, one MYH partner enhances the association of the other two partners to MYH. Moreover, APE1 and Hus1 act together to stabilize the MYH/SIRT6 complex. Within human cells, MYH and SIRT6 are efficiently recruited to confined oxidative DNA damage sites within transcriptionally active chromatin, but not within repressive chromatin. In addition, Myh foci induced by oxidative stress and Sirt6 depletion are frequently localized on mouse telomeres.</p><p>Although SIRT6, APE1, and 9-1-1 bind to the interdomain connector of MYH, they do not compete for MYH association. Our findings indicate that SIRT6 forms a complex with MYH, APE1, and 9-1-1 to maintain genomic and telomeric integrity in mammalian cells.</p>","PeriodicalId":497,"journal":{"name":"BMC Molecular Biology","volume":"16 1","pages":""},"PeriodicalIF":2.946,"publicationDate":"2015-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12867-015-0041-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"4461117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}