Regulation of Telomere Structure and Functions by Subunits of the INO80 Chromatin Remodeling Complex

ABSTRACT ATP-dependent chromatin remodeling complexes have been implicated in the regulation of transcription, replication, and more recently DNA double-strand break repair. Here we report that the Ies3p subunit of the Saccharomyces cerevisiae INO80 chromatin remodeling complex interacts with a conserved tetratricopeptide repeat domain of the telomerase protein Est1p. Deletion of IES3 and some other subunits of the complex induced telomere elongation and altered telomere position effect. In telomerase-negative mutants, loss of Ies3p delayed the emergence of recombinational survivors and stimulated the formation of extrachromosomal telomeric circles in survivors. Deletion of IES3 also resulted in heightened levels of telomere-telomere fusions in telomerase-deficient strains. In addition, a delay in survivor formation was observed in an Arp8p-deficient mutant. Because Arp8p is required for the chromatin remodeling activity of the INO80 complex, the complex may promote recombinational telomere maintenance by altering chromatin structure. Consistent with this notion, we observed preferential localization of multiple subunits of the INO80 complex to telomeres. Our results reveal novel functions for a subunit of the telomerase complex and the INO80 chromatin remodeling complex.

[1]  S. Gray The End of the End? , 2007, Current Anthropology.

[2]  C. Peterson,et al.  Interplay between Ino80 and Swr1 chromatin remodeling enzymes regulates cell cycle checkpoint adaptation in response to DNA damage. , 2006, Genes & development.

[3]  R. Wellinger,et al.  Telomerase- and capping-independent yeast survivors with alternate telomere states , 2006, Nature Cell Biology.

[4]  David Lydall,et al.  Linear chromosome maintenance in the absence of essential telomere-capping proteins , 2006, Nature Cell Biology.

[5]  C. Nugent,et al.  Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p , 2006, Nature Cell Biology.

[6]  Leonid Kruglyak,et al.  Telomere Length as a Quantitative Trait: Genome-Wide Survey and Genetic Mapping of Telomere Length-Control Genes in Yeast , 2006, PLoS genetics.

[7]  Michael K. Coleman,et al.  A Mammalian Chromatin Remodeling Complex with Similarities to the Yeast INO80 Complex* , 2005, Journal of Biological Chemistry.

[8]  M. Osley,et al.  Chromatin remodelling at a DNA double-strand break site in Saccharomyces cerevisiae , 2005, Nature.

[9]  S. Marcand,et al.  Rap1 prevents telomere fusions by nonhomologous end joining , 2005, The EMBO journal.

[10]  B. Cairns,et al.  Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair. , 2005, Genes & development.

[11]  C. Autexier,et al.  Telomerase can act as a template- and RNA-independent terminal transferase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Griffith,et al.  Recombination at Long Mutant Telomeres Produces Tiny Single- and Double-Stranded Telomeric Circles , 2005, Molecular and Cellular Biology.

[13]  Sang Eun Lee,et al.  The Yeast Chromatin Remodeler RSC Complex Facilitates End Joining Repair of DNA Double-Strand Breaks , 2005, Molecular and Cellular Biology.

[14]  Kou-Juey Wu,et al.  Extrachromosomal Telomeric Circles Contribute to Rad52-, Rad50-, and Polymerase δ-Mediated Telomere-Telomere Recombination in Saccharomyces cerevisiae , 2005, Eukaryotic Cell.

[15]  Barbara Hohn,et al.  Recruitment of the INO80 Complex by H2A Phosphorylation Links ATP-Dependent Chromatin Remodeling with DNA Double-Strand Break Repair , 2004, Cell.

[16]  N. Krogan,et al.  INO80 and γ-H2AX Interaction Links ATP-Dependent Chromatin Remodeling to DNA Damage Repair , 2004, Cell.

[17]  T. Fisher,et al.  Cell cycle-dependent regulation of yeast telomerase by Ku , 2004, Nature Structural &Molecular Biology.

[18]  J. Griffith,et al.  Telomeric DNA in ALT Cells Is Characterized by Free Telomeric Circles and Heterogeneous t-Loops , 2004, Molecular and Cellular Biology.

[19]  T. Lange,et al.  Homologous Recombination Generates T-Loop-Sized Deletions at Human Telomeres , 2004, Cell.

[20]  D. Dash,et al.  In silico characterization of the INO80 subfamily of SWI2/SNF2 chromatin remodeling proteins. , 2004, Biochemical and biophysical research communications.

[21]  B. Breitkreutz,et al.  A genome-wide telomere screen in yeast: the long and short of it all. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Martin Kupiec,et al.  A genome-wide screen for Saccharomyces cerevisiae deletion mutants that affect telomere length. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Jue Lin,et al.  Mutant telomere sequences lead to impaired chromosome separation and a unique checkpoint response. , 2004, Molecular biology of the cell.

[24]  T. Cech Beginning to Understand the End of the Chromosome , 2004, Cell.

[25]  Wei-Hua Wu,et al.  ATP-Driven Exchange of Histone H2AZ Variant Catalyzed by SWR1 Chromatin Remodeling Complex , 2004, Science.

[26]  Lynne Regan,et al.  TPR proteins: the versatile helix. , 2003, Trends in biochemical sciences.

[27]  P. Mieczkowski,et al.  Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[28]  T. Lange,et al.  DNA Damage Foci at Dysfunctional Telomeres , 2003, Current Biology.

[29]  B. Snow,et al.  Functional Conservation of the Telomerase Protein Est1p in Humans , 2003, Current Biology.

[30]  P. Bucher,et al.  A Human Homolog of Yeast Est1 Associates with Telomerase and Uncaps Chromosome Ends When Overexpressed , 2003, Current Biology.

[31]  P. Bucher,et al.  Telomere Maintenance in Fission Yeast Requires an Est1 Ortholog , 2003, Current Biology.

[32]  C. Greider,et al.  Short telomeres induce a DNA damage response in Saccharomyces cerevisiae. , 2003, Molecular biology of the cell.

[33]  J. Derisi,et al.  Telomeric protein distributions and remodeling through the cell cycle in Saccharomyces cerevisiae. , 2003, Molecular biology of the cell.

[34]  I. Mian,et al.  Analysis of Telomerase in Candida albicans: Potential Role in Telomere End Protection , 2002, Eukaryotic Cell.

[35]  S. Evans,et al.  The Est1 subunit of Saccharomyces cerevisiae telomerase makes multiple contributions to telomere length maintenance. , 2002, Genetics.

[36]  J. Lingner,et al.  Telomerase: biochemical considerations for enzyme and substrate. , 2002, Trends in biochemical sciences.

[37]  T. Cech,et al.  A bulged stem tethers Est1p to telomerase RNA in budding yeast. , 2002, Genes & development.

[38]  S. Teng,et al.  Est1p As a Cell Cycle-Regulated Activator of Telomere-Bound Telomerase , 2002, Science.

[39]  J. Berman,et al.  MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae. , 2002, Molecular biology of the cell.

[40]  R. Kingston,et al.  Cooperation between Complexes that Regulate Chromatin Structure and Transcription , 2002, Cell.

[41]  W. Tham,et al.  Transcriptional silencing at Saccharomyces telomeres: implications for other organisms , 2002, Oncogene.

[42]  E. Blackburn Switching and Signaling at the Telomere , 2001, Cell.

[43]  K. Dubrana,et al.  Turning telomeres off and on. , 2001, Current opinion in cell biology.

[44]  J. Hoeijmakers,et al.  Chromosomal stability and the DNA double-stranded break connection , 2001, Nature Reviews Genetics.

[45]  V. Lundblad,et al.  Cdc13 Delivers Separate Complexes to the Telomere for End Protection and Replication , 2001, Cell.

[46]  E. Blackburn,et al.  Telomere fusions caused by mutating the terminal region of telomeric DNA. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[47]  E. Blackburn,et al.  The end of the (DNA) line , 2000, Nature Structural Biology.

[48]  S. Teng,et al.  Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. , 2000, Molecular cell.

[49]  Ali Hamiche,et al.  A chromatin remodelling complex involved in transcription and DNA processing , 2000, Nature.

[50]  V. Zakian,et al.  The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. , 2000, Genes & development.

[51]  C. Greider,et al.  Recombination in telomere-length maintenance. , 2000, Trends in biochemical sciences.

[52]  Jerry L. Workman,et al.  ATP-Dependent Chromatin-Remodeling Complexes , 2000, Molecular and Cellular Biology.

[53]  S. Teng,et al.  Telomere-Telomere Recombination Is an Efficient Bypass Pathway for Telomere Maintenance in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[54]  G. Blatch,et al.  The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. , 1999, BioEssays : news and reviews in molecular, cellular and developmental biology.

[55]  T. Cech,et al.  Telomerase and the maintenance of chromosome ends. , 1999, Current opinion in cell biology.

[56]  V. Lundblad,et al.  The telomerase reverse transcriptase: components and regulation. , 1998, Genes & development.

[57]  H. Biessmann,et al.  Telomere maintenance without telomerase. , 1997, Chromosoma.

[58]  D. Morris,et al.  Est1 has the properties of a single-stranded telomere end-binding protein. , 1996, Genes & development.

[59]  S. Lavi,et al.  Induction of circles of heterogeneous sizes in carcinogen-treated cells: two-dimensional gel analysis of circular DNA molecules , 1996, Molecular and cellular biology.

[60]  D. Gottschling,et al.  TLC1: template RNA component of Saccharomyces cerevisiae telomerase. , 1994, Science.

[61]  E. Blackburn,et al.  An alternative pathway for yeast telomere maintenance rescues est1− senescence , 1993, Cell.

[62]  J. Szostak,et al.  A mutant with a defect in telomere elongation leads to senescence in yeast , 1989, Cell.

[63]  W. L. Fangman,et al.  The localization of replication origins on ARS plasmids in S. cerevisiae , 1987, Cell.

[64]  A M Olovnikov,et al.  A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. , 1973, Journal of theoretical biology.

[65]  Nevan J Krogan,et al.  INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. , 2004, Cell.