Potential of Data Integration to Identify Regulatory Snps in Late-Onset Alzheimer’S Disease GWAS Findings
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Figure 2S 4 7 A - C 080125 CSCs 080418 CSCs - + IFN-a 48 h + IFN-a 48 h + IFN-a 72 h 6 + IFN-a 72 h 3 5 MRFI 4 2 3 2 1 1 0 0 MHC I MHC II MICA MICB ULBP-1 ULBP-2 ULBP-3 ULBP-4 MHC I MHC II MICA MICB ULBP-1 ULBP-2 ULBP-3 ULBP-4 7 B 13 080125 FBS - D 080418 FBS - + IFN-a 48 h 12 + IFN-a 48 h + IFN-a 72 h + IFN-a 72 h 6 080125 FBS 11 10 5 9 8 4 7 6 3 MRFI 5 4 2 3 2 1 1 0 0 MHC I MHC II MICA MICB ULBP-1 ULBP-2 ULBP-3 ULBP-4 MHC I MHC II MICA MICB ULBP-1 ULBP-2 ULBP-3 ULBP-4 Molecule Molecule FIGURE 4S FIGURE 5S Panel A Panel B FIGURE 6S A B C D Supplemental Results Table 1S. Modulation by IFN-α of APM in GBM CSC and FBS tumor cell lines. Molecule * Cell line IFN-α‡ HLA β2-m# HLA LMP TAP1 TAP2 class II A A HC§ 2 7 10 080125 CSCs - 1∞ (1) 3 (65) 2 (91) 1 (2) 6 (47) 2 (61) 1 (3) 1 (2) 1 (3) + 2 (81) 11 (80) 13 (99) 1 (3) 8 (88) 4 (91) 1 (2) 1 (3) 2 (68) 080125 FBS - 2 (81) 4 (63) 4 (83) 1 (3) 6 (80) 3 (67) 2 (86) 1 (3) 2 (75) + 2 (99) 14 (90) 7 (97) 5 (75) 7 (100) 6 (98) 2 (90) 1 (4) 3 (87) 080418 CSCs - 2 (51) 1 (1) 1 (3) 2 (47) 2 (83) 2 (54) 1 (4) 1 (2) 1 (3) + 2 (81) 3 (76) 5 (75) 2 (50) 2 (83) 3 (71) 1 (3) 2 (87) 1 (2) 080418 FBS - 1 (3) 3 (70) 2 (88) 1 (4) 3 (87) 2 (76) 1 (3) 1 (3) 1 (2) + 2 (78) 7 (98) 5 (99) 2 (94) 5 (100) 3 (100) 1 (4) 2 (100) 1 (2) 070104 CSCs - 1 (2) 1 (3) 1 (3) 2 (78) 1 (3) 1 (2) 1 (3) 1 (3) 1 (2) + 2 (98) 8 (100) 10 (88) 4 (89) 3 (98) 3 (94) 1 (4) 2 (86) 2 (79) * expression of APM molecules was evaluated by intracellular staining and cytofluorimetric analysis; ‡ cells were treatead or not (+/-) for 72 h with 1000 IU/ml of IFN-α; # β-2 microglobulin; § β-2 microglobulin-free HLA-A heavy chain; ∞ values are indicated as ratio between the mean of fluorescence intensity of cells stained with the selected mAb and that of the negative control; bold values indicate significant MRFI (≥ 2). -
IDENTIFICATION of CELL SURFACE MARKERS WHICH CORRELATE with SALL4 in a B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA with T(8;14)
IDENTIFICATION of CELL SURFACE MARKERS WHICH CORRELATE WITH SALL4 in a B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA WITH T(8;14) DISCOVERED THROUGH BIOINFORMATIC ANALYSIS of MICROARRAY GENE EXPRESSION DATA The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:38962442 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA ,'(17,),&$7,21 2) &(// 685)$&( 0$5.(56 :+,&+ &255(/$7( :,7+ 6$// ,1 $ %&(// $&87( /<03+2%/$67,& /(8.(0,$ :,7+ W ',6&29(5(' 7+528*+ %,2,1)250$7,& $1$/<6,6 2) 0,&52$55$< *(1( (;35(66,21 '$7$ 52%(57 3$8/ :(,1%(5* $ 7KHVLV 6XEPLWWHG WR WKH )DFXOW\ RI 7KH +DUYDUG 0HGLFDO 6FKRRO LQ 3DUWLDO )XOILOOPHQW RI WKH 5HTXLUHPHQWV IRU WKH 'HJUHH RI 0DVWHU RI 0HGLFDO 6FLHQFHV LQ ,PPXQRORJ\ +DUYDUG 8QLYHUVLW\ %RVWRQ 0DVVDFKXVHWWV -XQH Thesis Advisor: Dr. Li Chai Author: Robert Paul Weinberg Department of Pathology Candidate MMSc in Immunology Brigham and Womens’ Hospital Harvard Medical School 77 Francis Street 25 Shattuck Street Boston, MA 02215 Boston, MA 02215 IDENTIFICATION OF CELL SURFACE MARKERS WHICH CORRELATE WITH SALL4 IN A B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA WITH TRANSLOCATION t(8;14) DISCOVERED THROUGH BIOINFORMATICS ANALYSIS OF MICROARRAY GENE EXPRESSION DATA Abstract Acute Lymphoblastic Leukemia (ALL) is the most common leukemia in children, causing signficant morbidity and mortality annually in the U.S. -
Regulation of DNA Cross-Link Repair by the Fanconi Anemia/BRCA Pathway
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Regulation of DNA cross-link repair by the Fanconi anemia/BRCA pathway Hyungjin Kim and Alan D. D’Andrea1 Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA The maintenance of genome stability is critical for sur- and quadradials, a phenotype widely used as a diagnostic vival, and its failure is often associated with tumorigen- test for FA. esis. The Fanconi anemia (FA) pathway is essential for At least 15 FA gene products constitute a common the repair of DNA interstrand cross-links (ICLs), and a DNA repair pathway, the FA pathway, which resolves germline defect in the pathway results in FA, a cancer ICLs encountered during replication (Fig. 1A). Specifi- predisposition syndrome driven by genome instability. cally, eight FA proteins (FANCA/B/C/E/F/G/L/M) form Central to this pathway is the monoubiquitination of a multisubunit ubiquitin E3 ligase complex, the FA core FANCD2, which coordinates multiple DNA repair activ- complex, which activates the monoubiquitination of ities required for the resolution of ICLs. Recent studies FANCD2 and FANCI after genotoxic stress or in S phase have demonstrated how the FA pathway coordinates three (Wang 2007). The FANCM subunit initiates the pathway critical DNA repair processes, including nucleolytic in- (Fig. 1B). It forms a heterodimeric complex with FAAP24 cision, translesion DNA synthesis (TLS), and homologous (FA-associated protein 24 kDa), and the complex resem- recombination (HR). Here, we review recent advances in bles an XPF–ERCC1 structure-specific endonuclease pair our understanding of the downstream ICL repair steps (Ciccia et al. -
Checkpoint Defects Require WRNIP1 to Counteract R-Loop-Associated
bioRxiv preprint doi: https://doi.org/10.1101/858761; this version posted November 29, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. CHECKPOINT DEFECTS REQUIRE WRNIP1 TO COUNTERACT R-LOOP- ASSOCIATED GENOMIC INSTABILITY Veronica Marabitti1, Giorgia Lillo1, Eva Malacaria1, Valentina Palermo1, Pietro Pichierri1 and Annapaola Franchitto1, * 1Department of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanita’, Viale Regina Elena 299, Rome, 00161, Italy * To whom correspondence should be addressed. Tel: +39 0649903042; Fax: +39 0649903650; Email: [email protected] Keywords: Werner syndrome, RECQ helicases, DNA repair, Replication stress 1 bioRxiv preprint doi: https://doi.org/10.1101/858761; this version posted November 29, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. ABSTRACT Conflicts between replication and transcription are common source of genome instability and many factors participate in prevention or removal of harmful R-loops. Here, we demonstrate that a WRNIP1-mediated response plays an important role in counteracting accumulation of aberrant R- loops. Using human cellular models with compromised ATR-dependent checkpoint activation, we show that WRNIP1 is stabilised in chromatin and is needed for maintaining genome integrity by mediating the ATM-dependent phosphorylation of CHK1. -
Leukaemia Section
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Leukaemia Section Mini Review t(11;11)(q14;q23) KMT2A/PICALM inv(11)(q14q23) KMT2A/PICALM Jean-Loup Huret Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France. jean- [email protected] Published in Atlas Database: March 2017 Online updated version : http://AtlasGeneticsOncology.org/Anomalies/t1111q14q23ID1411.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/68879/03-2017-t1111q14q23ID1411.pdf DOI: 10.4267/2042/68879 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2018 Atlas of Genetics and Cytogenetics in Oncology and Haematology Otherwise, in a large study of cases of chromosomal Abstract rearrangements involving the human KMT2A Review on t(11;11)(q14;q23) and inv(11)(q14q23) (MLL) gene, a t(11;11)(q14;q23) or inv(11)(q14q23) KMT2A/PICALM, with data on clinics and the KMT2A/PICALM was found in 1 out of 440 infant genes involved. ALL patients, 1 out of 105 infant AML patients, 1 KEYWORDS out of 205 pediatric ALL patients, 1 out of 272 adult Chromosome 11; KMT2A; PICALM; acute myeloid AML patients, and none in 202 pediatric AML leukemia; acute lymphoblastic leukemia. patients, nor in 333 adult ALL patients (Meyer et al., 2013). Note: the case by Meyer et al., 2006 was Clinics and pathology reused in Meyer et al., 2013. Disease Genes involved and Acute myeloid leukemia (AML) and acute proteins lymphoblastic leukemia (ALL). Clinics PICALM (clathrin assembly lymphoid myeloid leukemia gene) There was the case of a 12-week-old female infant with acute monocytic leukemia (M5b) and Location inv(11)(q14q23), dead at day 11 (Wechsler et al., 11q14.2 2003). -
Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives
cancers Review Targeting BCL-2 in Cancer: Advances, Challenges, and Perspectives Shirin Hafezi 1 and Mohamed Rahmani 1,2,* 1 Research Institute of Medical & Health Sciences, University of Sharjah, P.O. Box 27272 Sharjah, United Arab Emirates; [email protected] 2 Department of Basic Medical Sciences, College of Medicine, University of Sharjah, P.O. Box 27272 Sharjah, United Arab Emirates * Correspondence: [email protected]; Tel.: +971-6505-7759 Simple Summary: Apoptosis, a programmed form of cell death, represents the main mechanism by which cells die. Such phenomenon is highly regulated by the BCL-2 family of proteins, which includes both pro-apoptotic and pro-survival proteins. The decision whether cells live or die is tightly controlled by a balance between these two classes of proteins. Notably, the pro-survival Bcl-2 proteins are frequently overexpressed in cancer cells dysregulating this balance in favor of survival and also rendering cells more resistant to therapeutic interventions. In this review, we outlined the most important steps in the development of targeting the BCL-2 survival proteins, which laid the ground for the discovery and the development of the selective BCL-2 inhibitor venetoclax as a therapeutic drug in hematological malignancies. The limitations and future directions are also discussed. Abstract: The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapoptotic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins Citation: Hafezi, S.; Rahmani, M. -
Multivariate Meta-Analysis of Differential Principal Components Underlying Human Primed and Naive-Like Pluripotent States
bioRxiv preprint doi: https://doi.org/10.1101/2020.10.20.347666; this version posted October 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. October 20, 2020 To: bioRxiv Multivariate Meta-Analysis of Differential Principal Components underlying Human Primed and Naive-like Pluripotent States Kory R. Johnson1*, Barbara S. Mallon2, Yang C. Fann1, and Kevin G. Chen2*, 1Intramural IT and Bioinformatics Program, 2NIH Stem Cell Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA Keywords: human pluripotent stem cells; naive pluripotency, meta-analysis, principal component analysis, t-SNE, consensus clustering *Correspondence to: Dr. Kory R. Johnson ([email protected]) Dr. Kevin G. Chen ([email protected]) 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.10.20.347666; this version posted October 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. ABSTRACT The ground or naive pluripotent state of human pluripotent stem cells (hPSCs), which was initially established in mouse embryonic stem cells (mESCs), is an emerging and tentative concept. To verify this important concept in hPSCs, we performed a multivariate meta-analysis of major hPSC datasets via the combined analytic powers of percentile normalization, principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and SC3 consensus clustering. -
Análise Integrativa De Perfis Transcricionais De Pacientes Com
UNIVERSIDADE DE SÃO PAULO FACULDADE DE MEDICINA DE RIBEIRÃO PRETO PROGRAMA DE PÓS-GRADUAÇÃO EM GENÉTICA ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Ribeirão Preto – 2012 ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas Tese apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo para obtenção do título de Doutor em Ciências. Área de Concentração: Genética Orientador: Prof. Dr. Eduardo Antonio Donadi Co-orientador: Prof. Dr. Geraldo A. S. Passos Ribeirão Preto – 2012 AUTORIZO A REPRODUÇÃO E DIVULGAÇÃO TOTAL OU PARCIAL DESTE TRABALHO, POR QUALQUER MEIO CONVENCIONAL OU ELETRÔNICO, PARA FINS DE ESTUDO E PESQUISA, DESDE QUE CITADA A FONTE. FICHA CATALOGRÁFICA Evangelista, Adriane Feijó Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. Ribeirão Preto, 2012 192p. Tese de Doutorado apresentada à Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo. Área de Concentração: Genética. Orientador: Donadi, Eduardo Antonio Co-orientador: Passos, Geraldo A. 1. Expressão gênica – microarrays 2. Análise bioinformática por module maps 3. Diabetes mellitus tipo 1 4. Diabetes mellitus tipo 2 5. Diabetes mellitus gestacional FOLHA DE APROVAÇÃO ADRIANE FEIJÓ EVANGELISTA Análise integrativa de perfis transcricionais de pacientes com diabetes mellitus tipo 1, tipo 2 e gestacional, comparando-os com manifestações demográficas, clínicas, laboratoriais, fisiopatológicas e terapêuticas. -
(A) Co-IP of HA Tagged ARMC9 with Flag Tagged Interactors
Supplemental Figures Supplemental Figure 1 Validation of ARMC9 interactome. (A) Co-IP of HA tagged ARMC9 with Flag tagged interactors. HA tagged ARMC9 was transfected alone or in conjunction with Flag tagged interactor constructs, HA beads were used to pull down the bait construct and blots were probed for the presence of the Flag tagged interactors. Experiment was performed in biological triplicates. Full blots are viewable in Plemental Figure 10. (B) Single transfection of PalmMyr-CFP-ARMC9 (green) and (C) single transfection of mRFP-TOGARAM1 (red) shows the localization in the absence of the respective interactor. (D) Co-expression of mRFP-TOGARAM1 and PalmMyr-CFP-ARMC9 shows microtubule colocalization. Scale bar indicates 20 μm. 1 Supplemental Figure 2 In silico modeling of the TOG2 variants. (A) Ribbon model of the wild type TOG2 domain structure of TOGARAM1 generated using HOPE. The protein is colored by the following elements: alpha-helices are show in blue, beta-strand is shown in red, turns are green, 3/10 helix is yellow, and random coil is cyan. (B) p. Arg368Trp missense variant in the TOG2 domain in ribbon-presentation generated using HOPE. TOG2 is shown in grey, the side chain of the mutated residue is shown in magenta. (C) A close up of the side chain of both wild type and mutated residue is shown in green and red respectively. (D) Inverted view of wild type TOG2 domain structure of TOGARAM1 as compared to (a). (E) p.Leu375Pro missense variant modeled in the TOG2 domain of TOGARAM1 in ribbon-presentation. TOG2 is shown in grey, the side chain of the mutated residue is shown in magenta. -
A CRISPR-Based Screen for Hedgehog Signaling Provides Insights Into Ciliary Function and Ciliopathies
ARTICLES https://doi.org/10.1038/s41588-018-0054-7 A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies David K. Breslow 1,2,7*, Sascha Hoogendoorn 3,7, Adam R. Kopp2, David W. Morgens4, Brandon K. Vu2, Margaret C. Kennedy1, Kyuho Han4, Amy Li4, Gaelen T. Hess4, Michael C. Bassik4, James K. Chen 3,5* and Maxence V. Nachury 2,6* Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ -tubulin and ε -tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening. he primary cilium is a surface-exposed microtubule-based approach. Indeed, most studies to date have searched for genes that compartment that serves as an organizing center for diverse either intrinsically affect cell growth or affect sensitivity to applied Tsignaling pathways1–3. Mutations affecting cilia cause ciliopa- perturbations16–23. thies, a group of developmental disorders including Joubert syn- Here, we engineered a Hh-pathway-sensitive reporter to enable drome, Meckel syndrome (MKS), nephronophthisis (NPHP), and an antibiotic-based selection platform. -
Mir-17-92 Fine-Tunes MYC Expression and Function to Ensure
ARTICLE Received 31 Mar 2015 | Accepted 22 Sep 2015 | Published 10 Nov 2015 DOI: 10.1038/ncomms9725 OPEN miR-17-92 fine-tunes MYC expression and function to ensure optimal B cell lymphoma growth Marija Mihailovich1, Michael Bremang1, Valeria Spadotto1, Daniele Musiani1, Elena Vitale1, Gabriele Varano2,w, Federico Zambelli3, Francesco M. Mancuso1,w, David A. Cairns1,w, Giulio Pavesi3, Stefano Casola2 & Tiziana Bonaldi1 The synergism between c-MYC and miR-17-19b, a truncated version of the miR-17-92 cluster, is well-documented during tumor initiation. However, little is known about miR-17-19b function in established cancers. Here we investigate the role of miR-17-19b in c-MYC-driven lymphomas by integrating SILAC-based quantitative proteomics, transcriptomics and 30 untranslated region (UTR) analysis upon miR-17-19b overexpression. We identify over one hundred miR-17-19b targets, of which 40% are co-regulated by c-MYC. Downregulation of a new miR-17/20 target, checkpoint kinase 2 (Chek2), increases the recruitment of HuR to c- MYC transcripts, resulting in the inhibition of c-MYC translation and thus interfering with in vivo tumor growth. Hence, in established lymphomas, miR-17-19b fine-tunes c-MYC activity through a tight control of its function and expression, ultimately ensuring cancer cell homeostasis. Our data highlight the plasticity of miRNA function, reflecting changes in the mRNA landscape and 30 UTR shortening at different stages of tumorigenesis. 1 Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20139, Italy. 2 Units of Genetics of B cells and lymphomas, IFOM, FIRC Institute of Molecular Oncology Foundation, Milan 20139, Italy. -
Vertebrate WRNIP1 and BLM Are Required for Efficient Maintenance of Genome Stability
Genes Genet. Syst. (2008) 83, p. 95–100 Vertebrate WRNIP1 and BLM are required for efficient maintenance of genome stability Tomoko Hayashi1, Masayuki Seki1*, Eri Inoue1, Akari Yoshimura1, Yumiko Kusa1, Shusuke Tada1 and Takemi Enomoto1,2 1Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan 2Tohoku University 21st Century COE Program, “Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation,” Sendai, Miyagi 980-8578, Japan (Received 25 September 2007, accepted 15 November 2007) Bloom syndrome (BS) is rare autosomal recessive disorder associated with chro- mosomal instability. The gene responsible for BS, BLM, encodes a protein belonging to the RecQ helicase family. Disruptions of the SGS1 gene of Saccha- romyces cerevisiae, which encodes the RecQ helicase homologue in the budding yeast, causes accelerated aging, and this phenotype is enhanced by the disruption of MGS1, the budding yeast homologue for WRNIP1. To examine the functional relationship between RecQ and WRNIP1 in vertebrate cells, we generated and characterized wrnip1/blm cells derived from the chicken B-lymphocyte line DT40. wrnip1/blm cells showed an additive elevation of sister chromatid exchange (SCE), suggesting that both genes independently contribute to the suppression of excess SCE formation. The double mutants were more sensitive to DNA damage from camptothecin (CPT), but not to damage from methyl methanesulfonate, than either single mutant. This result suggests that WRNIP1 and BLM function inde- pendently to repair DNA or induce tolerance to the lesions induced by CPT. Key words: BLM, DT40, Mgs1, RecQ, WRN, WRNIP1 Five genes encoding RecQ helicase homologues have RecQL4 mutations result in RAPADILINO syndrome and been identified in human cells, three of which are the Baller-Gerold syndrome, suggesting that RecQL4 has mul- causative genes for Bloom syndrome (BS), Werner syn- tiple functions (Dietschy et al., 2007).