Ku complex controls the replication time of DNA in telomere regions.

We have investigated whether the Ku complex is involved in regulating DNA replication in the yeast Saccharomyces cerevisiae. We find that Ku proteins control the replication time of telomeric regions; replication origins located close to telomeres or within subtelomeric repeat sequences normally initiate late, but are activated much earlier in mutants lacking Ku function. In contrast, origins distant from telomeres initiate replication at the normal time. Ku is one of the first components identified as important for replication timing, and specification of the replication time of chromosome ends by Ku is consistent with its role in maintaining telomere localization.

[1]  John J. Wyrick,et al.  Genome-Wide Distribution of ORC and MCM Proteins in S. cerevisiae: High-Resolution Mapping of Replication Origins , 2001, Science.

[2]  M. Zannis‐Hadjopoulos,et al.  In vivo association of Ku with mammalian origins of DNA replication. , 2001, Molecular biology of the cell.

[3]  Ronald W. Davis,et al.  Replication dynamics of the yeast genome. , 2001, Science.

[4]  M. Hande,et al.  Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells , 2001, Current Biology.

[5]  J. Haber,et al.  Break-induced replication: A review and an example in budding yeast , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[6]  P. Silver,et al.  Localization of yeast telomeres to the nuclear periphery is separable from transcriptional repression and telomere stability functions. , 2001, Molecular cell.

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

[8]  D. Gilbert.  Nuclear Position Leaves Its Mark on Replication Timing , 2001, The Journal of cell biology.

[9]  S. Gasser,et al.  The Positioning and Dynamics of Origins of Replication in the Budding Yeast Nucleus , 2001, The Journal of cell biology.

[10]  D. Gottschling,et al.  The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku , 2001, Nature Genetics.

[11]  M. Hande,et al.  Ku acts in a unique way at the mammalian telomere to prevent end joining. , 2000, Genes & development.

[12]  B. Lehnert,et al.  DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Gilbert,et al.  The spatial position and replication timing of chromosomal domains are both established in early G1 phase. , 1999, Molecular cell.

[14]  D. Shore,et al.  Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by Rif proteins , 1999, Current Biology.

[15]  Sophie G. Martin,et al.  Relocalization of Telomeric Ku and SIR Proteins in Response to DNA Strand Breaks in Yeast , 1999, Cell.

[16]  S. Jackson,et al.  Ku, a DNA repair protein with multiple cellular functions? , 1999, Mutation research.

[17]  F. Pryde,et al.  Limitations of silencing at native yeast telomeres , 1999, The EMBO journal.

[18]  D. Gottschling,et al.  Telomeric chromatin modulates replication timing near chromosome ends. , 1999, Genes & development.

[19]  F. Cross,et al.  CLB5-dependent activation of late replication origins in S. cerevisiae. , 1998, Molecular cell.

[20]  Jian Li,et al.  The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities , 1998, Current Biology.

[21]  Edward J. Louis,et al.  Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres , 1998, Current Biology.

[22]  R. Wellinger,et al.  Yeast Ku as a regulator of chromosomal DNA end structure. , 1998, Science.

[23]  W. L. Fangman,et al.  Cdc7 is required throughout the yeast S phase to activate replication origins. , 1998, Genes & development.

[24]  J. Diffley,et al.  The Cdc7 protein kinase is required for origin firing during S phase. , 1998, Genes & development.

[25]  W. L. Fangman,et al.  Cell cycle-dependent establishment of a late replication program. , 1997, Science.

[26]  D. Rio,et al.  DNA double-strand-break sensitivity, DNA replication, and cell cycle arrest phenotypes of Ku-deficient Saccharomyces cerevisiae. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[27]  B. van Steensel,et al.  Structure, subnuclear distribution, and nuclear matrix association of the mammalian telomeric complex , 1996, The Journal of cell biology.

[28]  S. Eisenberg,et al.  The Ku-like protein from Saccharomyces cerevisiae is required in vitro for the assembly of a stable multiprotein complex at a eukaryotic origin of replication. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[29]  W. L. Fangman,et al.  Multiple determinants controlling activation of yeast replication origins late in S phase. , 1996, Genes & development.

[30]  B. J. Brewer,et al.  Analysis of replication intermediates by two-dimensional agarose gel electrophoresis. , 1995, Methods in enzymology.

[31]  E. Winnacker,et al.  A putative homologue of the human autoantigen Ku from Saccharomyces cerevisiae. , 1993, The Journal of biological chemistry.

[32]  W. L. Fangman,et al.  A position effect on the time of replication origin activation in yeast , 1992, Cell.

[33]  C. Newlon,et al.  Time of replication of ARS elements along yeast chromosome III , 1989, Molecular and cellular biology.

[34]  R. McCarroll,et al.  Time of replication of yeast centromeres and telomeres , 1988, Cell.

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

[36]  L. Hartwell,et al.  Macromolecule Synthesis in Temperature-sensitive Mutants of Yeast , 1967, Journal of bacteriology.