Aberrant Recombination and Repair During Immunoglobulin Class Switching in BRCA1-Deficient Human B Cells
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Homologous Repair of DNA Damage and Tumorigenesis: the BRCA Connection
Oncogene (2002) 21, 8981 – 8993 ª 2002 Nature Publishing Group All rights reserved 0950 – 9232/02 $25.00 www.nature.com/onc Homologous repair of DNA damage and tumorigenesis: the BRCA connection Maria Jasin*,1 1Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA Homologous recombination has been recognized in recent Tirkkonen et al., 1997; Turner et al., 2002; Xu et al., years to be an important DNA repair pathway in 1999), are sensitive to DNA damaging agents (Bhatta- mammalian cells, for such damage as chromosomal charyya et al., 2000; Connor et al., 1997; Gowen et al., double-strand breaks. Cells mutated for the genes 1998; Kraakman-van der Zwet et al., 2002; Morimatsu involved in the hereditary breast and ovarian cancer et al., 1998; Moynahan et al., 2001a; Scully et al., 1999; susceptibility syndromes, i.e. BRCA1 and BRCA2, show Sharan et al., 1997; Shen et al., 1998; Zhong et al., defects in DNA repair by homologous recombination, 1999), including ionizing radiation and cross-linking implicating this repair pathway in protecting individuals agents, and have elevated mutation rates (Kraakman- against tumorigenesis. This review summarizes recent van der Zwet et al., 2002; Tutt et al., 2002). During S advances in our understanding of BRCA1 and BRCA2 in phase or upon treatment of cells with DNA damaging DNA repair, as well as insight into these proteins agents or replication inhibitors, both proteins are in gleaned from structure determination of domains of these nuclear foci along with several other proteins involved proteins and the broader evolutionary conservation than in the damage response, including the DNA repair previously appreciated. -
(TEX) Genes: a Review Focused on Spermatogenesis and Male Fertility
Bellil et al. Basic and Clinical Andrology (2021) 31:9 https://doi.org/10.1186/s12610-021-00127-7 REVIEW ARTICLE Open Access Human testis-expressed (TEX) genes: a review focused on spermatogenesis and male fertility Hela Bellil1, Farah Ghieh2,3, Emeline Hermel2,3, Béatrice Mandon-Pepin2,3 and François Vialard1,2,3* Abstract Spermatogenesis is a complex process regulated by a multitude of genes. The identification and characterization of male-germ-cell-specific genes is crucial to understanding the mechanisms through which the cells develop. The term “TEX gene” was coined by Wang et al. (Nat Genet. 2001; 27: 422–6) after they used cDNA suppression subtractive hybridization (SSH) to identify new transcripts that were present only in purified mouse spermatogonia. TEX (Testis expressed) orthologues have been found in other vertebrates (mammals, birds, and reptiles), invertebrates, and yeasts. To date, 69 TEX genes have been described in different species and different tissues. To evaluate the expression of each TEX/tex gene, we compiled data from 7 different RNA-Seq mRNA databases in humans, and 4 in the mouse according to the expression atlas database. Various studies have highlighted a role for many of these genes in spermatogenesis. Here, we review current knowledge on the TEX genes and their roles in spermatogenesis and fertilization in humans and, comparatively, in other species (notably the mouse). As expected, TEX genes appear to have a major role in reproduction in general and in spermatogenesis in humans but also in all mammals such as the mouse. Most of them are expressed specifically or predominantly in the testis. -
Gene Expression Signature–Based Prognostic Risk Score in Patients with Primary Central Nervous System Lymphoma
Published OnlineFirst August 20, 2012; DOI: 10.1158/1078-0432.CCR-12-0596 Clinical Cancer Imaging, Diagnosis, Prognosis Research Gene Expression Signature–Based Prognostic Risk Score in Patients with Primary Central Nervous System Lymphoma Atsushi Kawaguchi1, Yasuo Iwadate2, Yoshihiro Komohara3, Masakazu Sano4, Koji Kajiwara5, Naoki Yajima4, Naoto Tsuchiya4, Jumpei Homma4, Hiroshi Aoki4, Tsutomu Kobayashi4, Yuko Sakai7, Hiroaki Hondoh6, Yukihiko Fujii4, Tatsuyuki Kakuma1, and Ryuya Yamanaka7 Abstract Purpose: Better understanding of the underlying biology of primary central nervous system lymphomas (PCNSL) is critical for the development of early detection strategies, molecular markers, and new therapeutics. This study aimed to define genes associated with survival of patients with PCNSL. Experimental Design: Expression profiling was conducted on 32 PCNSLs. A gene classifier was developed using the random survival forests model. On the basis of this, prognosis prediction score (PPS) using immunohistochemical analysis is also developed and validated in another data set with 43 PCNSLs. Results: We identified 23 genes in which expressions were strongly and consistently related to patient survival. A PPS was developed for overall survival (OS) using a univariate Cox model. Survival analyses using the selected 23-gene classifiers revealed a prognostic value for high-dose methotrexate (HD-MTX) and HD- MTX–containing polychemotherapy regimen–treated patients. Patients predicted to have good outcomes by the PPS showed significantly longer survival than those with poor predicted outcomes (P < 0.0001). PPS using immunohistochemical analysis is also significant in test (P ¼ 0.0004) and validation data set (P ¼ 0.0281). The gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P < 0.0001). -
Prognosis Value of RBBP8 Expression in Plasma Cell Myeloma
Cancer Gene Therapy https://doi.org/10.1038/s41417-018-0069-3 ARTICLE Prognosis value of RBBP8 expression in plasma cell myeloma 1 2 3 4 5 1 1 1 Weilong Zhang ● Ying Song ● Xue He ● Xiaoni Liu ● Ye Zhang ● Zuozhen Yang ● Ping Yang ● Jing Wang ● 1 4 3 4 1 Kai Hu ● Weiyou Liu ● Xiuru Zhang ● Xiaoliang Yuan ● Hongmei Jing Received: 30 July 2018 / Revised: 30 October 2018 / Accepted: 2 November 2018 © The Author(s) 2019. This article is published with open access Abstract Plasma cell myeloma (PCM) secretes monoclonal immunoglobulin (Ig) by clonal plasma cells of abnormal proliferation in the bone marrow. As PCM is incurable, it is necessary to find new biomarkers to predict the prognosis and recurrence of PCM. The relationship between cancer and RBBP8 has not been fully studied. The role of RBBP8 in tumorigenesis remains inconsistent. We described the expression of RBBP8 in the gene expression profile of 1930 PCM samples (1878 PCM patients) from seven independent data sets. We analyzed the relationship between RBBP8 and survival prognosis, recurrence, and treatment response in patients with PCM, and the biological significance of RBBP8 in PCM. The gene expression level of RBBP8 was significantly related to the International staging system (ISS) grade of PCM (P = 0.0012). RBBP8 expression in different molecular subtypes was different (P < 2.2e-16). High RBBP8 expression is associated with 1234567890();,: 1234567890();,: poor survival in PCM (P < 0.0001). High expression of RBBP8 indicates that PCM patients are more likely to relapse (P = 0.0078). The biological significance of RBBP8 in PCM is related to the cell cycle (P < 0.05). -
HCC and Cancer Mutated Genes Summarized in the Literature Gene Symbol Gene Name References*
HCC and cancer mutated genes summarized in the literature Gene symbol Gene name References* A2M Alpha-2-macroglobulin (4) ABL1 c-abl oncogene 1, receptor tyrosine kinase (4,5,22) ACBD7 Acyl-Coenzyme A binding domain containing 7 (23) ACTL6A Actin-like 6A (4,5) ACTL6B Actin-like 6B (4) ACVR1B Activin A receptor, type IB (21,22) ACVR2A Activin A receptor, type IIA (4,21) ADAM10 ADAM metallopeptidase domain 10 (5) ADAMTS9 ADAM metallopeptidase with thrombospondin type 1 motif, 9 (4) ADCY2 Adenylate cyclase 2 (brain) (26) AJUBA Ajuba LIM protein (21) AKAP9 A kinase (PRKA) anchor protein (yotiao) 9 (4) Akt AKT serine/threonine kinase (28) AKT1 v-akt murine thymoma viral oncogene homolog 1 (5,21,22) AKT2 v-akt murine thymoma viral oncogene homolog 2 (4) ALB Albumin (4) ALK Anaplastic lymphoma receptor tyrosine kinase (22) AMPH Amphiphysin (24) ANK3 Ankyrin 3, node of Ranvier (ankyrin G) (4) ANKRD12 Ankyrin repeat domain 12 (4) ANO1 Anoctamin 1, calcium activated chloride channel (4) APC Adenomatous polyposis coli (4,5,21,22,25,28) APOB Apolipoprotein B [including Ag(x) antigen] (4) AR Androgen receptor (5,21-23) ARAP1 ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1 (4) ARHGAP35 Rho GTPase activating protein 35 (21) ARID1A AT rich interactive domain 1A (SWI-like) (4,5,21,22,24,25,27,28) ARID1B AT rich interactive domain 1B (SWI1-like) (4,5,22) ARID2 AT rich interactive domain 2 (ARID, RFX-like) (4,5,22,24,25,27,28) ARID4A AT rich interactive domain 4A (RBP1-like) (28) ARID5B AT rich interactive domain 5B (MRF1-like) (21) ASPM Asp (abnormal -
Irregular Telomeres Impair Meiotic Synapsis and Recombination in Mice
Irregular telomeres impair meiotic synapsis and recombination in mice Lin Liu*†, Sonia Franco‡, Barbara Spyropoulos§, Peter B. Moens§, Maria A. Blasco‡, and David L. Keefe*†¶ *Department of Obstetrics and Gynecology, Brown Medical School, Women and Infants Hospital, Providence, RI 02905; †Laboratory for Reproductive Medicine, Marine Biological Laboratory, Woods Hole, MA 02543; ‡Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre, 28029 Madrid, Spain; and §Department of Biology, York University, North York, ON, Canada M3J 1P3 Edited by Mary-Lou Pardue, Massachusetts Institute of Technology, Cambridge, MA, and approved March 10, 2004 (received for review February 2, 2004) Telomere shortening can lead to chromosome instability, replica- central element at pachytene stage of meiotic prophase I (19– tive senescence, and apoptosis in both somatic and male germ cells. 22). Thus, the structure and number of SCP3 elements provide To study roles for mammalian telomeres in homologous pairing a key marker for evaluating synapsis between homologues. We and recombination, we characterized effects of telomere shorten- analyzed effects of telomere shortening in late-generation ing on spermatogenesis and oogenesis in late-generation telo- TRϪ/Ϫ female mice on meiotic chromosome synapsis and re- merase-deficient mice. We show that shortened telomeres of combination and compared them with males. Because very Ϫ/Ϫ late-generation telomerase-deficient mice impair meiotic synapsis late-generation (G6 or G7)TR male mice exhibit extensive and decrease recombination, in particular, in females. In response apoptosis in germ cells and sterility, we focused on intermediate Ϫ/Ϫ to telomere shortening, male germ cells mostly undergo apoptosis, generation (e.g., G4)TR mice, because these mice show whereas female germ cells preferentially arrest in early meiosis, telomere shortening, but less apoptosis and decreased fertility suggesting sexually dimorphic surveillance mechanisms for telo- (3, 14). -
TEX15 Associates with MILI and Silences Transposable Elements in Male Germ Cells
Downloaded from genesdev.cshlp.org on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH COMMUNICATION noncatalytic germ cell-specific paralog of DNMT3A/3B, TEX15 associates with MILI causes reactivation of TEs in male germ cells and loss and silences transposable of maternal genomic imprints, resulting in sterility (Bourc’his et al. 2001; Bourc’his and Bestor 2004). Loss of elements in male germ cells DNMT3C, a rodent and germ cell-specific de novo DNA methyltransferase, leads to reactivation of LINE1 and Fang Yang,1 Yemin Lan,2 Radha Raman Pandey,3 3 2 IAP retrotransposons (Barau et al. 2016). In addition to David Homolka, Shelley L. Berger, DNA methylation, repressive histone modifications Ramesh S. Pillai,3 Marisa S. Bartolomei,2 (H3K9me2 and H3K9me3) are important for silencing of and P. Jeremy Wang1 transposable elements (Di Giacomo et al. 2013; Liu et al. 2014; Pezic et al. 2014; Zamudio et al. 2015). 1Department of Biomedical Sciences, University of Pennsylvania The piRNA (Piwi-associated small noncoding RNAs) School of Veterinary Medicine, Philadelphia, Pennsylvania pathway is an evolutionarily conserved RNA-based TE si- 19104, USA; 2Epigenetics Institute, Department of Cell and lencing mechanism in the germline (Siomi et al. 2011). Developmental Biology, Perelman School of Medicine, piRNAs are mostly derived from TEs in early germ cells University of Pennsylvania, Philadelphia, Pennsylvania 19104, (Aravin et al. 2008; Kuramochi-Miyagawa et al. 2010). Ge- USA; 3Department of Molecular Biology, Science III, University nome-wide demethylation in primordial germ cells of Geneva, CH-1211 Geneva 4, Switzerland (PGCs) causes a burst of TE expression (Bourc’his and Bes- tor 2004). -
Table S1 Primers Used for Genomic DNA Sequencing of K-Ras and TP53
Table S1 Primers used for genomic DNA sequencing of K-Ras and TP53 Gene, exon Forward primer Reverse primer k-Ras, exon 1 GTTCTAATATAGTCACATTT ACTCATGAAAATGGTCAGAGAAACCTTTAT k-Ras, exon 2 GAAGTAAAAGGTGCACTGTA AACTATAATTACTCCTTAAT TP53, exon 4 AGGACCTGGTCCTCTGAC CTGGGAAGGGACAGAAGA TP53, exon 5 TGACTTTCAACTCTGTCTCCT TCAGTGAGGAATCAGAGGCC TP53, exon 6 CTGGAGAGACGACAGAGGCC CCAGAGACCCCAGTTGCAAAC TP53, exon 7 AAGGCGCACTGGCCTCATCTT CGCCGGAAATGTGATGAGAG TP53, exon 8 TGGTTGGGAGTAGATGGAGCC CACCGCTTCTTGTCCTGCTT TP53, exon 9 GTGGAGGAGACCAAGGGTGCA AGGTAAAACAGTCAAGAAGAA Table S2. Genes in cytogenetic band with recurrent copy number alterations Gains Cytoband Gene Protein name Cytoband Gene Protein name 1 q42.2 KIAA1383 KIAA1383 18 q11.1-11.2 KIAA1772 KIAA1772 establishment of cohesion 1 homolog 1 (S. 1 q42.2 C1orf57 chromosome 1 open reading frame 57 18 q11.1-11.2 ESCO1 cerevisiae) 1 q42.2 PCNXL2 pecanex-like 2 (Drosophila) 18 q11.1-11.2 SNRPD1 small nuclear ribonucleoprotein D1 polypeptide 1 q42.2 KIAA1804 mixed lineage kinase 4 18 q11.1-11.2 ABHD3 abhydrolase domain containing 3 11 q13.1 SLC25A45 solute carrier family 25, member 45 18 q11.1-11.2 MIB1 mindbomb homolog 1 (Drosophila) 11 q13.1 FRMD8 FERM domain containing 8 18 q11.1-11.2 GATA6 GATA binding protein 6 11 q13.1 NCRNA00084 non-protein coding RNA 84 18 q11.1-11.2 CTAGE1 cutaneous T-cell lymphoma-associated antigen 1 metastasis associated lung adenocarcinoma 11 q13.1 MALAT1 18 q11.1-11.2 RBBP8 retinoblastoma binding protein 8 transcript 1 (non-protein coding) 20 q13.13 CEBPB CCAAT/enhancer -
Dissertation Meiotic Recombination and Synapsis
DISSERTATION MEIOTIC RECOMBINATION AND SYNAPSIS IN WILD-TYPE AND ASYNAPTIC MUTANTS OF TOMATO (SOLANUM LYCOPERSICUM) Submitted by Huanyu Qiao Department of Biology In partial fulfillment of the requirements For the Degree of Doctor of Philosophy Colorado State University Fort Collins, Colorado Fall 2010 Doctoral Committee: Department Chair: Daniel Bush Advisor: Lorinda Anderson Co-advisor: Stephen Stack Pat Bedinger Rajinder Ranu ABSTRACT MEIOTIC RECOMBINATION AND SYNAPSIS IN WILD-TYPE AND ASYNAPTIC MUTANTS OF TOMATO (SOLANUM LYCOPERSICUM) Recombination nodules (RNs) and synaptonemal complexes (SCs) are meiosis-specific structures that play important roles in crossing over. During pachytene, RNs mark crossover sites along SCs. MLH1, a mismatch repair protein, promotes crossing over and is a component of most RNs. In wild-type tomato, each bivalent has one, two or three crossovers (=chiasmata), and the number and distribution of these crossovers is affected by crossover interference (the tendency for one crossover to reduce the likelihood of another crossover nearby). Although the phenomenon of genetic interference was discovered nearly one hundred years ago, its molecular basis is still unknown. SCs occur between pairs of homologous chromosomes (bivalents) during prophase I and consist of two parallel rod-like lateral elements held together by transverse fibers. Each lateral element is associated with the two sister chromatids of one of the homologous chromosomes. Cohesin complexes consisting of four proteins (SMC1, SMC3, SYN1/REC8 and SCC3) are found in lateral elements and link sister chromatids together. My research addressed the question of how synapsis (SC formation) is related to the frequency and control of crossing over using tomato, particularly the as1 meiotic mutant, as a model system. -
Expression Analysis of Genes Encoding TEX11, TEX12, TEX14 and TEX15 in Testis Tissues of Men with Non-Obstructive Azoospermia
JBRA Assisted Reproduction 2018;00(0):000-000 doi: 10.5935/1518-0557.20180030 Original article Expression analysis of genes encoding TEX11, TEX12, TEX14 and TEX15 in testis tissues of men with non-obstructive azoospermia Parnaz Borjian Boroujeni1, Marjan Sabbaghian2, Mehdi Totonchi1,3, Niloofar Sodeifi2, Homa Sarkardeh1, Azam Samadian3, Mohammad Ali Sadighi-Gilani2,4, Hamid Gourabi1 1Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 2Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran 3Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran 4Department of Urology, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran Congresses where the study was presented: Middle East Fertility Society (MEFS) congress 2012, 2013 Royan International Twin Congress 2013, 2014 ABSTRACT Previous studies have revealed that TEX11, TEX12, Objective: Spermatogenesis is a complex process con- TEX14 and TEX15 expression is restricted to germ cells trolled by a plethora of genes. Changes in expression and and is not detectable in somatic tissues of humans and function of these genes may thus lead to spermatogenic mice (Wang et al., 2001; Adelman & Petrini, 2008). Mul- deficiency and male infertility. TEX11, TEX12, TEX14 and tiple studies have shown that X-linked germ cell-specif- TEX15 are germ cell-specific genes expressed in the tes- ic genes such as testis-expressed gene 11 (Tex11) have tis. TEX11, involved in the initiation and maintenance of significant roles in regulating male fertility (Zheng et al., chromosome synapses in meiotic chromosomes, has been 2010; Matzuk & Lamb, 2008). -
Supplemental Material.Pdf
Supplemental Material ZNF750 Interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 Chromatin Regulators to Repress Epidermal Progenitor Genes and Induce Differentiation Genes Lisa D. Boxer, Brook Barajas, Shiying Tao, Jiajing Zhang, and Paul Khavari Supplemental Inventory Figure S1. This figure supports Figure 1 and shows the Gene Ontology terms for ZNF750-bound but unaffected genes, the genomic enrichment of ZNF750 ChIP-seq peaks, and the percentage of peaks that contain the ZNF750 motif. Figure S2. This figure supports Figure 2 and shows gene expression changes with depletion of ZNF750-interacting proteins, confirms the knock-down of ZNF750-interacting proteins, and shows the quantification of Ki67 in ZNF750-interacting protein depleted organotypic tissue. Figure S3. This figure supports Figure 3 and shows the quantification of ZNF750 and interacting protein co-IPs, and IPs and Far western blots demonstrating competition between KLF4 and KDM1A for binding to ZNF750. Figure S4. This figure supports Figure 4 and shows the expression of ZNF750 mutant proteins and the effects of full-length or mutant ZNF750 on differentiation in organotypic tissue and on clonogenic growth. Figure S5. This figure supports Figure 5 and shows the effects of mutagenesis of ZNF750 and KLF4 motifs on reporter activity, and the changes in histone marks with depletion of ZNF750 and interacting proteins. Figure S6. This figure supports Figure 6 and shows the changes in mRNA and protein expression of ZNF750-interacting proteins during keratinocyte differentiation, and the expression of ZNF750-interacting proteins with ZNF750 depletion. Table S1. Supports Figure 1 and shows the genomic coordinates of ZNF750 ChIP-seq peaks. -
Prognosis Value of RBBP8 Expression in Plasma Cell Myeloma
Cancer Gene Therapy (2020) 27:22–29 https://doi.org/10.1038/s41417-018-0069-3 ARTICLE Prognosis value of RBBP8 expression in plasma cell myeloma 1 2 3 4 5 1 1 1 Weilong Zhang ● Ying Song ● Xue He ● Xiaoni Liu ● Ye Zhang ● Zuozhen Yang ● Ping Yang ● Jing Wang ● 1 4 3 4 1 Kai Hu ● Weiyou Liu ● Xiuru Zhang ● Xiaoliang Yuan ● Hongmei Jing Received: 30 July 2018 / Revised: 30 October 2018 / Accepted: 2 November 2018 / Published online: 9 January 2019 © The Author(s) 2019. This article is published with open access Abstract Plasma cell myeloma (PCM) secretes monoclonal immunoglobulin (Ig) by clonal plasma cells of abnormal proliferation in the bone marrow. As PCM is incurable, it is necessary to find new biomarkers to predict the prognosis and recurrence of PCM. The relationship between cancer and RBBP8 has not been fully studied. The role of RBBP8 in tumorigenesis remains inconsistent. We described the expression of RBBP8 in the gene expression profile of 1930 PCM samples (1878 PCM patients) from seven independent data sets. We analyzed the relationship between RBBP8 and survival prognosis, recurrence, and treatment response in patients with PCM, and the biological significance of RBBP8 in PCM. The gene expression level of RBBP8 was significantly related to the International staging system (ISS) grade of PCM (P = 0.0012). RBBP8 expression in different molecular subtypes was different (P < 2.2e-16). High RBBP8 expression is associated with 1234567890();,: 1234567890();,: poor survival in PCM (P < 0.0001). High expression of RBBP8 indicates that PCM patients are more likely to relapse (P = 0.0078).