Histone H4 dosage modulates DNA damage response in the pathogenic yeast Candida glabrata via homologous recombination pathway

PLoS Genetics
Kundan KumarRupinder Kaur

Abstract

Candida glabrata, a nosocomial fungal bloodstream pathogen, causes significant morbidity and mortality in hospitals worldwide. The ability to replicate in macrophages and survive a high level of oxidative stress contributes to its virulence in the mammalian host. However, the role of DNA repair and recombination mechanisms in its pathobiology is still being discovered. Here, we have characterized the response of C. glabrata to the methyl methanesulfonate (MMS)-induced DNA damage. We found that the MMS exposure triggered a significant downregulation of histone H4 transcript and protein levels, and that, the damaged DNA was repaired by the homologous recombination (HR) pathway. Consistently, the reduced H4 gene dosage was associated with increased HR frequency and elevated resistance to MMS. The genetic analysis found CgRad52, a DNA strand exchange-promoter protein of the HR system, to be essential for this MMS resistance. Further, the tandem-affinity purification and mass spectrometry analysis revealed a substantially smaller interactome of H4 in MMS-treated cells. Among 23 identified proteins, we found the WD40-repeat protein CgCmr1 to interact genetically and physically with H4, and regulate H4 levels, HR pathway and MMS stres...Continue Reading

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Citations

Jun 20, 2020·Current Genetics·Kundan KumarRupinder Kaur

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Datasets Mentioned

BETA
GSE142737
PXD016867

Methods Mentioned

BETA
thermal
PCR
RNA-Seq
histone acetylation
pull-down
affinity purification

Software Mentioned

YGOB
Clustal Omega
ImageJ
GO
Slim Mapper
Sequest
GraphPad Prism
Kallisto
DESeq
BLASTP

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