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

Area of Science:

• Molecular Biology
• Genetics
• DNA Repair Mechanisms

Background:

• Nucleosomes act as barriers to DNA repair, hindering enzymes like nucleotide excision repair (NER).
• Chromatin remodelers, including RSC and SWI/SNF, are known to facilitate DNA access by altering nucleosome positions.
• Both RSC and SWI/SNF have been previously implicated in NER pathways in yeast.

Purpose of the Study:

• To investigate the genome-wide roles of RSC and SWI/SNF chromatin remodelers in repairing UV-induced DNA damage.
• To elucidate the specific contributions of RSC and SWI/SNF to NER and base excision repair (BER) in different genomic contexts.
• To define the functional interplay between chromatin remodeling and DNA repair subpathways.

Main Methods:

• Generation of genome-wide repair maps for UV-induced cyclobutane pyrimidine dimers (CPDs) in yeast mutants lacking RSC or SWI/SNF.
• Analysis of DNA repair defects in nucleosomal DNA, linker DNA, and nucleosome-free regions (NFRs).
• Assessment of RSC's role in transcription-coupled NER (TC-NER) and base excision repair (BER) of N-methylpurine (NMP) lesions.

Main Results:

• SWI/SNF is not broadly required for NER but facilitates CPD repair at specific genes.
• RSC is crucial for general NER across the genome, including nucleosomal, linker, and NFRs.
• RSC also impacts BER of NMP lesions and plays a direct role in TC-NER of transcribed DNA.

Conclusions:

• RSC is a vital facilitator of DNA repair, essential for both NER and BER pathways in various genomic locations.
• SWI/SNF has a more specialized role in NER at specific gene loci.
• These findings delineate the distinct roles of RSC and SWI/SNF in chromatin remodeling for DNA repair.