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  • 1. Bayne, Elizabeth H.
    et al.
    Portoso, Manuela
    Kagansky, Alexander
    Kos-Braun, Isabelle C.
    Urano, Takeshi
    Ekwall, Karl
    Södertörn University, School of Life Sciences.
    Alves, Flavia
    Rappsilber, Juri
    Allshire, Robin C.
    Splicing factors facilitate RNAi-directed silencing in fission yeast2008In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 322, no 5901, p. 602-606Article in journal (Refereed)
    Abstract [en]

    Heterochromatin formation at fission yeast centromeres is directed by RNA interference (RNAi). Noncoding transcripts derived from centromeric repeats are processed into small interfering RNAs (siRNAs) that direct the RNA-induced transcriptional silencing (RITS) effector complex to engage centromer transcripts, resulting in recruitment of the histone H3 lysine 9 methyltransferase Clr4, and hence silencing. We have found that defects in specific splicing factors, but not splicing itself, affect the generation of centromeric siRNAs and consequently centromeric heterochromatin integrity. Moreover, splicing factors physically associate with Cid12, a component of the RNAi machinery, and with centromeric chromatin, consistent with a direct role in RNAi. We propose that spliceosomal complexes provide a platform for siRNA generation and hence facilitate effective centromere repeat silencing.

  • 2.
    Djupedal, Ingela
    et al.
    Södertörn University, School of Life Sciences.
    Ekwall, Karl
    Södertörn University, School of Life Sciences.
    Molecular biology - The paradox of silent heterochromatin2008In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 320, no 5876, p. 624-625Article in journal (Other academic)
  • 3.
    Dumanski, Jan P
    et al.
    Uppsala University.
    Rasi, Chiara
    Uppsala University.
    Lönn, Mikael
    Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology.
    Davies, Hanna
    Uppsala University.
    Ingelsson, Martin
    Uppsala University.
    Giedraitis, Vilmantas
    Uppsala University.
    Lannfelt, Lars
    Uppsala University.
    Magnusson, Patrik K E
    Karolinska Institutet.
    Lindgren, Cecilia M
    Morris, Andrew P
    University of Liverpool, Liverpool, UK..
    Cesarini, David
    New York University, New York, USA..
    Johannesson, Magnus
    Stockholm School of Economics.
    Tiensuu Janson, Eva
    Uppsala University.
    Lind, Lars
    Uppsala University.
    Pedersen, Nancy L
    Karolinska Institutet.
    Ingelsson, Erik
    Uppsala University.
    Forsberg, Lars A
    Uppsala University.
    Smoking is associated with mosaic loss of chromosome Y2015In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 347, no 6217, p. 81-83Article in journal (Refereed)
    Abstract [en]

    Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% CI = 2.8-6.7; ULSAM: OR = 2.4, 95% CI = 1.6-3.6; and PIVUS: OR = 3.5, 95% CI = 1.4-8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.

  • 4. Rhind, Nicholas
    et al.
    Chen, Zehua
    Yassour, Moran
    Thompson, Dawn A.
    Haas, Brian J.
    Habib, Naomi
    Wapinski, Ilan
    Roy, Sushmita
    Lin, Michael F.
    Heiman, David I.
    Young, Sarah K.
    Furuya, Kanji
    Guo, Yabin
    Pidoux, Alison
    Chen, Huei Mei
    Robbertse, Barbara
    Goldberg, Jonathan M.
    Aoki, Keita
    Bayne, Elizabeth H.
    Berlin, Aaron M.
    Desjardins, Christopher A.
    Dobbs, Edward
    Dukaj, Livio
    Fan, Lin
    FitzGerald, Michael G.
    French, Courtney
    Gujja, Sharvari
    Hansen, Klavs
    Keifenheim, Dan
    Levin, Joshua Z.
    Mosher, Rebecca A.
    Mueller, Carolin A.
    Pfiffner, Jenna
    Priest, Margaret
    Russ, Carsten
    Smialowska, Agata
    Södertörn University, School of Life Sciences, Molecular biology.
    Swoboda, Peter
    Sykes, Sean M.
    Vaughn, Matthew
    Vengrova, Sonya
    Yoder, Ryan
    Zeng, Qiandong
    Allshire, Robin
    Baulcombe, David
    Birren, Bruce W.
    Brown, William
    Ekwall, Karl
    Södertörn University, School of Life Sciences, Molecular biology.
    Kellis, Manolis
    Leatherwood, Janet
    Levin, Henry
    Margalit, Hanah
    Martienssen, Rob
    Nieduszynski, Conrad A.
    Spatafora, Joseph W.
    Friedman, Nir
    Dalgaard, Jacob Z.
    Baumann, Peter
    Niki, Hironori
    Regev, Aviv
    Nusbaum, Chad
    Comparative Functional Genomics of the Fission Yeasts2011In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 332, no 6032, p. 930-936Article in journal (Refereed)
    Abstract [en]

    The fission yeast clade-comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus-occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.

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