The elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents

Qing Li, A. M. Fazly, Hui Zhou, Shengbing Huang, Zhiguo Zhang, Bruce Stillman

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Histone chaperones CAF-1 and Asf1 function to deposit newly synthesized histones onto replicating DNA to promote nucleosome formation in a proliferating cell nuclear antigen (PCNA) dependent process. The DNA replication- or DNA repair-coupled nucleosome assembly pathways are important for maintenance of transcriptional gene silencing and genome stability. However, how these pathways are regulated is not well understood. Here we report an interaction between the Elongator histone acetyltransferase and the proliferating cell nuclear antigen. Cells lacking Elp3 (Kacetyltransferase Kat9), the catalytic subunit of the six-subunit Elongator complex, partially lose silencing of reporter genes at the chromosome VIIL telomere and at the HMR locus, and are sensitive to the DNA replication inhibitor hydroxyurea (HU) and the damaging agent methyl methanesulfonate (MMS). Like deletion of the ELP3, mutation of each of the four other subunits of the Elongator complex as well as mutations in Elp3 that compromise the formation of the Elongator complex also result in loss of silencing and increased HU sensitivity. Moreover, Elp3 is required for S-phase progression in the presence of HU. Epistasis analysis indicates that the elp3D mutant, which itself is sensitive to MMS, exacerbates the MMS sensitivity of cells lacking histone chaperones Asf1, CAF-1 and the H3 lysine 56 acetyltransferase Rtt109. The elp3D mutant has allele specific genetic interactions with mutations in POL30 that encodes PCNA and PCNA binds to the Elongator complex both in vivo and in vitro. Together, these results uncover a novel role for the intact Elongator complex in transcriptional silencing and maintenance of genome stability, and it does so in a pathway linked to the DNA replication and DNA repair protein PCNA.

Original languageEnglish (US)
Article numbere1000684
JournalPLoS Genetics
Volume5
Issue number10
DOIs
StatePublished - Oct 2009

Fingerprint

proliferating cell nuclear antigen
Proliferating Cell Nuclear Antigen
antigen
DNA damage
DNA Damage
methyl methanesulfonate
Methyl Methanesulfonate
hydroxyurea
Hydroxyurea
DNA
DNA replication
Histone Chaperones
damage
DNA Replication
histones
nucleosomes
Nucleosomes
Genomic Instability
mutation
DNA repair

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)

Cite this

The elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents. / Li, Qing; Fazly, A. M.; Zhou, Hui; Huang, Shengbing; Zhang, Zhiguo; Stillman, Bruce.

In: PLoS Genetics, Vol. 5, No. 10, e1000684, 10.2009.

Research output: Contribution to journalArticle

Li, Qing ; Fazly, A. M. ; Zhou, Hui ; Huang, Shengbing ; Zhang, Zhiguo ; Stillman, Bruce. / The elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents. In: PLoS Genetics. 2009 ; Vol. 5, No. 10.
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