Skip to main content
Article thumbnail
Location of Repository

Histone H3 Lys79 methylation is required for efficient nucleotide excision repair in a silenced locus of Saccharomyces cerevisiae

By Shubho Chaudhuri, John J. Wyrick and Michael J. Smerdon

Abstract

Methylation of specific histone lysine residues regulates gene expression and heterochromatin function, but little is known about its role in DNA repair. To examine how changes in conserved methylated residues of histone H3 affect nucleotide excision repair (NER), viable H3K4R and H3K79R mutants were generated in Saccharomyces cerevisiae. These mutants show decreased UV survival and impaired NER at the transcriptionally silent HML locus, while maintaining normal NER in the constitutively expressed RPB2 gene and transcriptionally repressed, nucleosome loaded GAL10 gene. Moreover, the HML chromatin in these mutants has reduced accessibility to Micrococcal nuclease (MNase). Importantly, chromatin immunoprecipitation analysis demonstrates there is enhanced recruitment of the Sir complex at the HML locus of these mutants, and deletion of the SIR2 or SIR3 genes restores the MNase accessibility and DNA repair efficiency at this locus. Furthermore, following UV irradiation expression of NER genes in these mutants remains at wild type levels, with the exception of RAD16 which decreases by more than 2-fold. These results indicate that impaired NER occurs in the silenced chromatin of H3K79R and H3K4,79R mutants as a result of increased binding of Sir complexes, which may reduce DNA lesion accessibility to repair enzymes

Topics: Genome Integrity, Repair and Replication
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:2655692
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2002). A core nucleosome surface crucial for transcriptional silencing.
    2. (2008). A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast.
    3. (1999). Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase.
    4. (2004). Cellular machineries for chromosomal DNA repair.
    5. (1993). Chromatin analysis in yeast using NP-40 permeabilised sphaeroplasts.
    6. (1995). Chromatin structure snap-shots: rapid nuclease digestion of chromatin in yeast.
    7. (2001). Common themes in mechanisms of gene silencing.
    8. (2002). COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression.
    9. (2005). Complicated tails: histone modifications and the DNA damage response.
    10. (1990). Differential repair of UV damage in rad mutants of Saccharomyces cerevisiae: a possible function of G2 arrest upon UV irradiation.
    11. (1989). Differential repair of UV damage in Saccharomyces cerevisiae.
    12. (1985). DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall.
    13. (2002). Dot1p modulates silencing in yeast by methylation of the nucleosome core.
    14. (2001). Highly specific antibodies determine histone acetylation site usage in yeast heterochromatin and euchromatin.
    15. (2007). Histone modifications in response to DNA damage.
    16. (1999). In vivo cross-linking and immunoprecipitation for studying dynamic Protein:DNA associations in a chromatin environment.
    17. (1994). Interaction of the yeast RAD7 and SIR3 proteins: implications for DNA repair and chromatin structure.
    18. (1999). Light and dark in chromatin repair: repair of UV-induced DNA lesions by photolyase and nucleotide excision repair.
    19. (2002). Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.
    20. (2003). Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: a potential mechanism for position-effect variegation.
    21. (2004). Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks.
    22. (2004). Methylation of H3 lysine 4at euchromatin promotes Sir3p association with heterochromatin.
    23. (2007). Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
    24. (2004). Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage.
    25. (2006). Molecular mechanisms of mammalian global genome nucleotide excision repair.
    26. (2005). Nucleotide excision repair in chromatin and the right of entry.
    27. (2005). Nucleotide excision repair in chromatin: the shape of things to come.
    28. (2000). Nucleotide excision repair in yeast.
    29. (1992). Preferential repair of cyclobutane pyrimidine dimers in the transcribed strand of a gene in yeast chromosomes and plasmids is dependent on transcription.
    30. (2004). Redundant roles for histone H3N-terminal lysine residues in subtelomeric gene repression in Saccharomyces cerevisiae.
    31. (2004). Regulated nucleosome mobility and the histone code.
    32. (1995). Regulation of the Saccharomyces cerevisiae DNA repair gene RAD16.
    33. (2005). Repair of UV lesions in nucleosomes–intrinsic properties and remodeling.
    34. (2003). Repair of UV lesions in silenced chromatin provides in vivo evidence for a compact chromatin structure.
    35. (2008). Saccharomyces cerevisiae Rad16 mediates ultraviolet-dependent histone H3 acetylation required for efficient global genome nucleotide-excision repair.
    36. (1987). Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene.
    37. (2007). Simultaneous mutation of methylated lysine residues in histone H3 causes enhanced gene silencing, cell cycle defects, and cell lethality in Saccharomyces cerevisiae.
    38. (2006). Structural basis for the methylation state-specific recognition of histone
    39. (2003). Structure and dynamic behavior of nucleosomes.
    40. (2001). Structure of the yeast nucleosome core particle reveals fundamental changes in internucleosome interactions.
    41. (2005). The DNA damage checkpoint response requires histone H2B ubiquitination by Rad6-Bre1 and H3 methylation by Dot1.
    42. (2003). The establishment, inheritance, and function of silenced chromatin in Saccharomyces cerevisiae.
    43. (2006). The LRS and SIN domains: two structurally equivalent but functionally distinct nucleosomal surfaces required for transcriptional silencing.
    44. (1994). The RAD7 and RAD16 genes, which are essential for pyrimidine dimer removal from the silent mating type loci, are also required for repair of the nontranscribed strand of an active gene in Saccharomyces cerevisiae.
    45. (2001). Translating the histone code.
    46. (2005). UV irradiation stimulates histone acetylation and chromatin remodeling at a repressed yeast locus.
    47. (2008). UV sensitive mutations in histone H3 in Saccharomyces cerevisiae that alter specific K79 methylation states genetically act through distinct DNA repair pathways.
    48. (2001). UV-damaged DNA-binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation.
    49. (2002). When repair meets chromatin. First in series on chromatin dynamics.
    50. (1999). Yeast autonomously replicating sequence binding factor is involved in nucleotide excision repair.
    51. (1997). Yeast Rad7-Rad16 complex, specific for the nucleotide excision repair of the nontranscribed DNA strand, is an ATP-dependent DNA damage sensor.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.