A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast

Ronita Nag, Feng Gong, Deirdre Fahy, Michael J. Smerdon

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Single amino acid changes at specific DNA contacts of histones H3 and H4 generate SWI/SNF-independent (Sin) mutants in yeast. We have analyzed the effect of the Sin mutation at R45 of histone H4 on cell survival following UV irradiation, nucleotide excision repair (NER) and chromatin structure. We find that this mutation renders yeast cells more resistant to UV damage and enhances NER at specific chromatin loci. In the transcriptionally silent HML, repressed GAL10 and the constitutively active RPB2 loci, H4 R45 mutants exhibit enhanced repair of UV-induced cyclobutane pyrimidine dimers (CPDs) compared to wild-type (wt). However, the H4 R45 mutation does not increase the transcription of NER genes, disrupt transcriptional silencing of the HML locus or alter repression in the GAL10 locus. We have further shown that the H4 R45C mutation increases the accessibility of nucleosome DNA in chromatin to exogenous nucleases and may expedite nucleosome rearrangements during NER. Taken together, our results indicate that the increased repair observed in Sin mutants is a direct effect of the altered chromatin landscape caused by the mutation, suggesting that such subtle changes in the conserved histone residues can influence the accessibility of DNA repair factors in chromatin.

Original languageEnglish
Pages (from-to)3857-3866
Number of pages10
JournalNucleic Acids Research
Volume36
Issue number11
DOIs
StatePublished - Jun 1 2008

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DNA Repair
Histones
Chromatin
Yeasts
Amino Acids
Mutation
Nucleosomes
Pyrimidine Dimers
DNA
Cell Survival
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast. / Nag, Ronita; Gong, Feng; Fahy, Deirdre; Smerdon, Michael J.

In: Nucleic Acids Research, Vol. 36, No. 11, 01.06.2008, p. 3857-3866.

Research output: Contribution to journalArticle

Nag, Ronita ; Gong, Feng ; Fahy, Deirdre ; Smerdon, Michael J. / A single amino acid change in histone H4 enhances UV survival and DNA repair in yeast. In: Nucleic Acids Research. 2008 ; Vol. 36, No. 11. pp. 3857-3866.
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