Distinct roles for RSC and SWI/SNF chromatin remodelers in genomic excision repair.

Nucleosomes are a significant barrier to the repair of UV damage because they impede damage recognition by nucleotide excision repair (NER). The RSC and SWI/SNF chromatin remodelers function in cells to promote DNA access by moving or evicting nucleosomes, and both have been linked to NER in yeast. Here, we report genome-wide repair maps of UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast cells lacking RSC or SWI/SNF activity.

CysHis Zinc Finger Methyl-CpG Binding Proteins: Getting a Handle on Methylated DNA.

DNA methylation is an essential epigenetic modification involved in the maintenance of genomic stability, preservation of cellular identity, and regulation of the transcriptional landscape needed to maintain cellular function. In an increasing number of disease conditions, DNA methylation patterns are inappropriately distributed in a manner that supports the disease phenotype. Methyl-CpG binding proteins (MBPs) are specialized transcription factors that read and translate methylated DNA signals into recruitment of protein assemblies that can alter local chromatin architecture and transcription.

Using Yeast as a Model Organism to Study the Functional Roles of Histone Acetylation in DNA Excision Repair.

Histone acetylation plays important roles in regulating DNA metabolic processes, including many DNA repair pathways. The nucleotide excision repair (NER) pathway is critical for removing bulky, helix-distorting DNA lesions, such as UV light-induced photoproducts, but the activity of this pathway is significantly inhibited when lesions reside in nucleosomes. Recent studies have indicated that histone acetyltransferase (HAT) activity may be induced in response to UV damage, in order to facilitate the repair of UV-induced lesions in chromatin.

NuA4 acetyltransferase is required for efficient nucleotide excision repair in yeast.

The nucleotide excision repair (NER) pathway is critical for removing damage induced by ultraviolet (UV) light and other helix-distorting lesions from cellular DNA. While efficient NER is critical to avoid cell death and mutagenesis, NER activity is inhibited in chromatin due to the association of lesion-containing DNA with histone proteins. Histone acetylation has emerged as an important mechanism for facilitating NER in chromatin, particularly acetylation catalyzed by the Spt-Ada-Gcn5 acetyltransferase (SAGA); however, it is not known if other histone acetyltransferases (HATs) promote NER activity in chromatin.

Residues in the Nucleosome Acidic Patch Regulate Histone Occupancy and Are Important for FACT Binding in .

The essential histone chaperone FACT plays a critical role in DNA replication, repair, and transcription, primarily by binding to histone H2A-H2B dimers and regulating their assembly into nucleosomes. While FACT histone chaperone activity has been extensively studied, the exact nature of the H2A and H2B residues important for FACT binding remains controversial. In this study, we characterized the functions of residues in the histone H2A and H2B acidic patch, which is important for binding many chromatin-associated factors.

A basic domain in the histone H2B N-terminal tail is important for nucleosome assembly by FACT.

Nucleosome assembly in vivo requires assembly factors, such as histone chaperones, to bind to histones and mediate their deposition onto DNA. In yeast, the essential histone chaperone FACT (FAcilitates Chromatin Transcription) functions in nucleosome assembly and H2A-H2B deposition during transcription elongation and DNA replication. Recent studies have identified candidate histone residues that mediate FACT binding to histones, but it is not known which histone residues are important for FACT to deposit histones onto DNA during nucleosome assembly.

Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae.

A critical feature of the intermolecular contacts that bind DNA to the histone octamer is the series of histone arginine residues that insert into the DNA minor groove at each superhelical location where the minor groove faces the histone octamer. One of these "sprocket" arginine residues, histone H4 R45, significantly affects chromatin structure in vivo and is lethal when mutated to alanine or cysteine in Saccharomyces cerevisiae (budding yeast). However, the roles of the remaining sprocket arginine residues (H3 R63, H3 R83, H2A R43, H2B R36, H2A R78, H3 R49) in chromatin structure and other cellular processes have not been well characterized.