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  1. Article: DNA polymerase family X: function, structure, and cellular roles.

    Yamtich, Jennifer / Sweasy, Joann B

    Biochimica et biophysica acta

    2009  Volume 1804, Issue 5, Page(s) 1136–1150

    Abstract: The X family of DNA polymerases in eukaryotic cells consists of terminal transferase and DNA polymerases beta, lambda, and mu. These enzymes have similar structural portraits, yet different biochemical properties, especially in their interactions with ... ...

    Abstract The X family of DNA polymerases in eukaryotic cells consists of terminal transferase and DNA polymerases beta, lambda, and mu. These enzymes have similar structural portraits, yet different biochemical properties, especially in their interactions with DNA. None of these enzymes possesses a proofreading subdomain, and their intrinsic fidelity of DNA synthesis is much lower than that of a polymerase that functions in cellular DNA replication. In this review, we discuss the similarities and differences of three members of Family X: polymerases beta, lambda, and mu. We focus on biochemical mechanisms, structural variation, fidelity and lesion bypass mechanisms, and cellular roles. Remarkably, although these enzymes have similar three-dimensional structures, their biochemical properties and cellular functions differ in important ways that impact cellular function.
    MeSH term(s) Animals ; DNA/metabolism ; DNA-Directed DNA Polymerase/chemistry ; DNA-Directed DNA Polymerase/physiology ; Humans
    Chemical Substances DNA (9007-49-2) ; DNA polymerase X (EC 2.7.7.-) ; DNA-Directed DNA Polymerase (EC 2.7.7.7)
    Language English
    Publishing date 2009-07-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbapap.2009.07.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: piRNA-like small RNAs mark extended 3'UTRs present in germ and somatic cells.

    Yamtich, Jennifer / Heo, Seok-Jin / Dhahbi, Joseph / Martin, David I K / Boffelli, Dario

    BMC genomics

    2015  Volume 16, Page(s) 462

    Abstract: Background: Piwi-interacting RNAs (piRNAs) are a class of small RNAs; distinct types of piRNAs are expressed in the mammalian testis at different stages of development. The function of piRNAs expressed in the adult testis is not well established. We ... ...

    Abstract Background: Piwi-interacting RNAs (piRNAs) are a class of small RNAs; distinct types of piRNAs are expressed in the mammalian testis at different stages of development. The function of piRNAs expressed in the adult testis is not well established. We conducted a detailed characterization of piRNAs aligning at or near the 3' UTRs of protein-coding genes in a deep dataset of small RNAs from adult mouse testis.
    Results: We identified 2710 piRNA clusters associated with 3' UTRs, including 1600 that overlapped genes not previously associated with piRNAs. 35% of the clusters extend beyond the annotated transcript; we find that these clusters correspond to, and are likely derived from, novel polyadenylated mRNA isoforms that contain previously unannotated extended 3'UTRs. Extended 3' UTRs, and small RNAs derived from them, are also present in somatic tissues; a subset of these somatic 3'UTR small RNA clusters are absent in mice lacking MIWI2, indicating a role for MIWI2 in the metabolism of somatic small RNAs.
    Conclusions: The finding that piRNAs are processed from extended 3' UTRs suggests a role for piRNAs in the remodeling of 3' UTRs. The presence of both clusters and extended 3'UTRs in somatic cells, with evidence for involvement of MIWI2, indicates that this pathway is more broadly distributed than currently appreciated.
    MeSH term(s) 3' Untranslated Regions/genetics ; Animals ; Argonaute Proteins/genetics ; Male ; Mice ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; Testis/metabolism
    Chemical Substances 3' Untranslated Regions ; Argonaute Proteins ; PIWIL4 protein, mouse ; RNA, Messenger ; RNA, Small Interfering
    Language English
    Publishing date 2015-06-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2041499-7
    ISSN 1471-2164 ; 1471-2164
    ISSN (online) 1471-2164
    ISSN 1471-2164
    DOI 10.1186/s12864-015-1662-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A germline polymorphism of DNA polymerase beta induces genomic instability and cellular transformation.

    Yamtich, Jennifer / Nemec, Antonia A / Keh, Agnes / Sweasy, Joann B

    PLoS genetics

    2012  Volume 8, Issue 11, Page(s) e1003052

    Abstract: Several germline single nucleotide polymorphisms (SNPs) have been identified in the POLB gene, but little is known about their cellular and biochemical impact. DNA Polymerase β (Pol β), encoded by the POLB gene, is the main gap-filling polymerase ... ...

    Abstract Several germline single nucleotide polymorphisms (SNPs) have been identified in the POLB gene, but little is known about their cellular and biochemical impact. DNA Polymerase β (Pol β), encoded by the POLB gene, is the main gap-filling polymerase involved in base excision repair (BER), a pathway that protects the genome from the consequences of oxidative DNA damage. In this study we tested the hypothesis that expression of the POLB germline coding SNP (rs3136797) in mammalian cells could induce a cancerous phenotype. Expression of this SNP in both human and mouse cells induced double-strand breaks, chromosomal aberrations, and cellular transformation. Following treatment with an alkylating agent, cells expressing this coding SNP accumulated BER intermediate substrates, including single-strand and double-strand breaks. The rs3136797 SNP encodes the P242R variant Pol β protein and biochemical analysis showed that P242R protein had a slower catalytic rate than WT, although P242R binds DNA similarly to WT. Our results suggest that people who carry the rs3136797 germline SNP may be at an increased risk for cancer susceptibility.
    MeSH term(s) Animals ; Cell Line ; Cell Transformation, Neoplastic ; Chromosome Aberrations ; DNA Breaks, Double-Stranded ; DNA Breaks, Single-Stranded ; DNA Damage/genetics ; DNA Polymerase beta/genetics ; DNA Polymerase beta/metabolism ; DNA Repair/genetics ; Disease Susceptibility ; Gene Expression Regulation ; Genomic Instability/genetics ; Germ Cells ; Humans ; Mice ; Oxidative Stress ; Polymorphism, Single Nucleotide/genetics
    Chemical Substances DNA Polymerase beta (EC 2.7.7.7)
    Language English
    Publishing date 2012-11-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1003052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Population-specific variation in haplotype composition and heterozygosity at the POLB locus.

    Yamtich, Jennifer / Speed, William C / Straka, Eva / Kidd, Judith R / Sweasy, Joann B / Kidd, Kenneth K

    DNA repair

    2009  Volume 8, Issue 5, Page(s) 579–584

    Abstract: DNA polymerase beta plays a central role in base excision repair (BER), which removes large numbers of endogenous DNA lesions from each cell on a daily basis. Little is currently known about germline polymorphisms within the POLB locus, making it ... ...

    Abstract DNA polymerase beta plays a central role in base excision repair (BER), which removes large numbers of endogenous DNA lesions from each cell on a daily basis. Little is currently known about germline polymorphisms within the POLB locus, making it difficult to study the association of variants at this locus with human diseases such as cancer. Yet, approximately thirty percent of human tumor types show variants of DNA polymerase beta. We have assessed the global frequency distributions of coding and common non-coding SNPs in and flanking the POLB gene for a total of 14 sites typed in approximately 2400 individuals from anthropologically defined human populations worldwide. We have found a marked difference between haplotype frequencies in African populations and in non-African populations.
    MeSH term(s) Adult ; DNA Polymerase beta/genetics ; Genetics, Population ; Haplotypes/genetics ; Humans ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide/genetics ; Population Groups/genetics
    Chemical Substances DNA Polymerase beta (EC 2.7.7.7)
    Language English
    Publishing date 2009-01-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2071608-4
    ISSN 1568-7856 ; 1568-7864
    ISSN (online) 1568-7856
    ISSN 1568-7864
    DOI 10.1016/j.dnarep.2008.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Development of coupling controlled polymerizations by adapter-ligation in mate-pair sequencing for detection of various genomic variants in one single assay.

    Dong, Zirui / Zhao, Xia / Li, Qiaoling / Yang, Zhenjun / Xi, Yang / Alexeev, Andrei / Shen, Hanjie / Wang, Ou / Ruan, Jie / Ren, Han / Wei, Hanmin / Qi, Xiaojuan / Li, Jiguang / Zhu, Xiaofan / Zhang, Yanyan / Dai, Peng / Kong, Xiangdong / Kirkconnell, Killeen / Alferov, Oleg /
    Giles, Shane / Yamtich, Jennifer / Kermani, Bahram G / Dong, Chao / Liu, Pengjuan / Mi, Zilan / Zhang, Wenwei / Xu, Xun / Drmanac, Radoje / Choy, Kwong Wai / Jiang, Yuan

    DNA research : an international journal for rapid publication of reports on genes and genomes

    2019  Volume 26, Issue 4, Page(s) 313–325

    Abstract: The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter- ... ...

    Abstract The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter-ligation reaction 3' branch ligation, we evidenced that CP-AL significantly increased DNA circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ∼50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.
    MeSH term(s) Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Genotyping Techniques/methods ; Humans ; Infertility, Male/genetics ; Male ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/methods
    Language English
    Publishing date 2019-05-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 1212508-8
    ISSN 1756-1663 ; 1340-2838
    ISSN (online) 1756-1663
    ISSN 1340-2838
    DOI 10.1093/dnares/dsz011
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  6. Article: Site-specific Genome Editing in PBMCs With PLGA Nanoparticle-delivered PNAs Confers HIV-1 Resistance in Humanized Mice.

    Schleifman, Erica B / McNeer, Nicole Ali / Jackson, Andrew / Yamtich, Jennifer / Brehm, Michael A / Shultz, Leonard D / Greiner, Dale L / Kumar, Priti / Saltzman, W Mark / Glazer, Peter M

    Molecular therapy. Nucleic acids

    2013  Volume 2, Page(s) e135

    Abstract: Biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating triplex-forming peptide nucleic acids (PNAs) and donor DNAs for recombination-mediated editing of the CCR5 gene were synthesized for delivery into human peripheral ... ...

    Abstract Biodegradable poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulating triplex-forming peptide nucleic acids (PNAs) and donor DNAs for recombination-mediated editing of the CCR5 gene were synthesized for delivery into human peripheral blood mononuclear cells (PBMCs). NPs containing the CCR5-targeting molecules efficiently entered PBMCs with low cytotoxicity. Deep sequencing revealed that a single treatment with the formulation resulted in a targeting frequency of 0.97% in the CCR5 gene and a low off-target frequency of 0.004% in the CCR2 gene, a 216-fold difference. NP-treated PBMCs efficiently engrafted immunodeficient NOD-scid IL-2rγ(-/-) mice, and the targeted CCR5 modification was detected in splenic lymphocytes 4 weeks posttransplantation. After infection with an R5-tropic strain of HIV-1, humanized mice with CCR5-NP-treated PBMCs displayed significantly higher levels of CD4(+) T cells and significantly reduced plasma viral RNA loads compared with control mice engrafted with mock-treated PBMCs. This work demonstrates the feasibility of PLGA-NP-encapsulated PNA-based gene-editing molecules for the targeted modification of CCR5 in human PBMCs as a platform for conferring HIV-1 resistance.Molecular Therapy-Nucleic Acids (2013) 2, e135; doi:10.1038/mtna.2013.59; published online 19 November 2013.
    Language English
    Publishing date 2013-11-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1038/mtna.2013.59
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