Regulation of rtt107 recruitment to stalled DNA replication forks by the cullin rtt101 and the rtt109 acetyltransferase.

RTT107 (ESC4, YHR154W) encodes a BRCA1 C-terminal domain protein that is important for recovery from DNA damage during S phase. Rtt107 is a substrate of the checkpoint kinase Mec1, and it forms complexes with DNA repair enzymes, including the nuclease subunit Slx4, but the role of Rtt107 in the DNA damage response remains unclear. We find that Rtt107 interacts with chromatin when cells are treated with compounds that cause replication forks to arrest. This damage-dependent chromatin binding requires the acetyltransferase Rtt109, but it does not require acetylation of the known Rtt109 target, histone H3-K56. Chromatin binding of Rtt107 also requires the cullin Rtt101, which seems to play a direct role in Rtt107 recruitment, because the two proteins are found in complex with each other. Finally, we provide evidence that Rtt107 is bound at or near stalled replication forks in vivo. Together, these results indicate that Rtt109, Rtt101, and Rtt107, which genetic evidence suggests are functionally related, form a DNA damage response pathway that recruits Rtt107 complexes to damaged or stalled replication forks.

[1]  Ronald W. Davis,et al.  A high-resolution atlas of nucleosome occupancy in yeast , 2007, Nature Genetics.

[2]  Junhong Han,et al.  Acetylation of Lysine 56 of Histone H3 Catalyzed by RTT109 and Regulated by ASF1 Is Required for Replisome Integrity* , 2007, Journal of Biological Chemistry.

[3]  P. Russell,et al.  Mms22 Preserves Genomic Integrity During DNA Replication in Schizosaccharomyces pombe , 2007, Genetics.

[4]  Katsuhiko Shirahige,et al.  Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. , 2007, Genes & development.

[5]  J. Haber,et al.  Phosphorylation of Slx4 by Mec1 and Tel1 Regulates the Single-Strand Annealing Mode of DNA Repair in Budding Yeast , 2007, Molecular and Cellular Biology.

[6]  P. Pasero,et al.  Maintenance of fork integrity at damaged DNA and natural pause sites. , 2007, DNA repair.

[7]  Junhong Han,et al.  The Rtt109-Vps75 Histone Acetyltransferase Complex Acetylates Non-nucleosomal Histone H3* , 2007, Journal of Biological Chemistry.

[8]  L. Selth,et al.  Vps75, A New Yeast Member of the NAP Histone Chaperone Family* , 2007, Journal of Biological Chemistry.

[9]  Grant W. Brown,et al.  Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map , 2007, Nature.

[10]  Michael A. Freitas,et al.  Histone H3-K56 acetylation is catalyzed by histone chaperone-dependent complexes. , 2007, Molecular cell.

[11]  J. Haber,et al.  Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses , 2007, Science.

[12]  Junhong Han,et al.  Rtt109 Acetylates Histone H3 Lysine 56 and Functions in DNA Replication , 2007, Science.

[13]  Robert Driscoll,et al.  Yeast Rtt109 Promotes Genome Stability by Acetylating Histone H3 on Lysine 56 , 2007, Science.

[14]  J. Connelly,et al.  Rtt107/Esc4 binds silent chromatin and DNA repair proteins using different BRCT motifs , 2006, BMC Molecular Biology.

[15]  Nancy L. Maas,et al.  Taking It Off: Regulation of H3 K56 Acetylation by Hst3 and Hst4 , 2006, Cell cycle.

[16]  Simon Tavaré,et al.  Genome-wide mapping of ORC and Mcm2p binding sites on tiling arrays and identification of essential ARS consensus sequences in S. cerevisiae , 2006, BMC Genomics.

[17]  Craig J. Benham,et al.  OriDB: a DNA replication origin database , 2006, Nucleic Acids Res..

[18]  Katsuhiko Shirahige,et al.  Establishment of sister chromatid cohesion at the S. cerevisiae replication fork. , 2006, Molecular cell.

[19]  J. Boeke,et al.  The Sirtuins Hst3 and Hst4p Preserve Genome Integrity by Controlling Histone H3 Lysine 56 Deacetylation , 2006, Current Biology.

[20]  Nancy L. Maas,et al.  Cell cycle and checkpoint regulation of histone H3 K56 acetylation by Hst3 and Hst4. , 2006, Molecular cell.

[21]  W. Heyer,et al.  Esc4/Rtt107 and the control of recombination during replication. , 2006, DNA repair.

[22]  B. Garcia,et al.  Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[23]  M. Peter,et al.  The Cullin Rtt101p Promotes Replication Fork Progression through Damaged DNA and Natural Pause Sites , 2006, Current Biology.

[24]  P. Russell,et al.  Rad22Rad52-dependent repair of ribosomal DNA repeats cleaved by Slx1-Slx4 endonuclease. , 2006, Molecular biology of the cell.

[25]  David Collingwood,et al.  Genomic mapping of single-stranded DNA in hydroxyurea-challenged yeasts identifies origins of replication , 2006, Nature Cell Biology.

[26]  M. Lopes,et al.  Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. , 2006, Molecular cell.

[27]  Grant W. Brown,et al.  Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. , 2005, Molecular biology of the cell.

[28]  J. Rouse,et al.  Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage. , 2005, The Biochemical journal.

[29]  S. Harvey,et al.  Brc1-Mediated DNA Repair and Damage Tolerance , 2005, Genetics.

[30]  P. Kaufman,et al.  Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C. , 2005, Genes & development.

[31]  P. Russell,et al.  The DNA damage response: sensing and signaling. , 2004, Current opinion in cell biology.

[32]  Jiri Bartek,et al.  Cell-cycle checkpoints and cancer , 2004, Nature.

[33]  J. Rouse Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage , 2004, The EMBO journal.

[34]  J. Yates,et al.  Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast. , 2003, Molecular biology of the cell.

[35]  Mitsuko Masutani,et al.  A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. , 2003, Nucleic acids research.

[36]  Katsuhiko Shirahige,et al.  S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex , 2003, Nature.

[37]  S. Brill,et al.  Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. , 2003, Genes & development.

[38]  Stephen J. Elledge,et al.  Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes , 2003, Science.

[39]  Charles Boone,et al.  A genome-wide screen for methyl methanesulfonate-sensitive mutants reveals genes required for S phase progression in the presence of DNA damage , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[40]  A. Carr DNA structure dependent checkpoints as regulators of DNA repair. , 2002, DNA repair.

[41]  S. Elledge,et al.  Checking on the fork: the DNA-replication stress-response pathway. , 2002, Trends in cell biology.

[42]  S. Brill,et al.  Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae , 2002, Current Genetics.

[43]  Floyd E Romesberg,et al.  Previously uncharacterized genes in the UV- and MMS-induced DNA damage response in yeast , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[44]  D. Toczyski,et al.  A unified view of the DNA-damage checkpoint. , 2002, Current opinion in cell biology.

[45]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[46]  Gary D Bader,et al.  Systematic Genetic Analysis with Ordered Arrays of Yeast Deletion Mutants , 2001, Science.

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

[48]  M. Curcio,et al.  Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae have conserved roles in genome maintenance. , 2001, Genetics.

[49]  J. Diffley,et al.  Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint , 2001, Nature.

[50]  P. Plevani,et al.  Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase , 1999, The EMBO journal.

[51]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

[52]  J. Boeke,et al.  Designer deletion strains derived from Saccharomyces cerevisiae S288C: A useful set of strains and plasmids for PCR‐mediated gene disruption and other applications , 1998, Yeast.

[53]  K. Nasmyth,et al.  Cohesins: Chromosomal Proteins that Prevent Premature Separation of Sister Chromatids , 1997, Cell.

[54]  O. Aparicio,et al.  Components and Dynamics of DNA Replication Complexes in S. cerevisiae: Redistribution of MCM Proteins and Cdc45p during S Phase , 1997, Cell.

[55]  J. Mornon,et al.  From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair , 1997, FEBS letters.

[56]  Peer Bork,et al.  A superfamily of conserved domains in DNA damage‐ responsive cell cycle checkpoint proteins , 1997, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[57]  Eugene V. Koonin,et al.  …Functional motifs… , 1996, Nature Genetics.

[58]  S. Elledge,et al.  Regulation of RAD53 by the ATM-Like Kinases MEC1 and TEL1 in Yeast Cell Cycle Checkpoint Pathways , 1996, Science.

[59]  J. Diffley,et al.  Two steps in the assembly of complexes at yeast replication origins in vivo , 1994, Cell.

[60]  L. Hartwell,et al.  Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. , 1994, Genes & development.

[61]  Rodney Rothstein,et al.  Elevated recombination rates in transcriptionally active DNA , 1989, Cell.

[62]  H. Aburatani,et al.  Genomic approach for the understanding of dynamic aspect of chromosome behavior. , 2006, Methods in enzymology.

[63]  S F Altschul,et al.  BRCA1 protein products ... Functional motifs... , 1996, Nature genetics.

[64]  F. Sherman Getting started with yeast. , 1991, Methods in enzymology.