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Analysis of alkylation damage formation and base excision repair at yeast transcription factor binding sites

ABSTRACT: Analysis of alkylation damage formation and base excision repair at yeast transcription factor binding sites

PROVIDER: PRJNA761418 | ENA |

REPOSITORIES: ENA

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Analysis of alkylation damage formation and base excision repair at yeast transcription factor binding sites

Project description:DNA base damage arises frequently in all living cells and is an important contributor to mutations and genome instability. The main repair pathway for base damage is base excision repair (BER). How the formation and repair of base lesions are modulated by DNA-binding proteins is poorly understood. Here we used a high-throughput damage mapping method, N-methylpurine-sequencing (NMP-seq), to characterize alkylation damage distribution and BER at yeast transcription factor (TF) binding sites upon the treatment with alkylating agent methyl methanesulfonate (MMS). We found that formation of alkylation damage was mainly suppressed at the binding sites of yeat TFs Abf1 and Reb1, but individual hotspots with elevated damage formation were also observed. Furthermore, our data indicates that repair of alkyhlation damage by BER was significantly inhibited both within the TF core motif and its adajcent DNA. The modulation of damage formation and BER was caused by the TF binding, because lesion formation and repair can be restored by depletion of Abf1 or Reb1 from the nucleus. Finally, we show that repair of UV damage by nucleotide excision repair (NER) was also inhibited at the binding sites of Abf1 and Reb1. A comparision between alkylyation and UV damage repair reveals that NER was inhibited in a broader DNA region relative to BER. Thus, our analyses indicate that TF binding significantly modulates alkylation damage formation and inhibits repair by the BER pathway. The interplay between base damage formation and BER may play an important role in affecting mutation frequency in gene regulatory regions.

2021-12-31 | GSE183622 | GEO

Expression data from yeast with modulated expression of base excision repair players

2007-11-30 | GSE9295 | GEO

Transcription profiling of S. cerevisiae with modulated expression of base excision repair players

Project description:We are investigating the transcriptional response of yeast to modulation of the expression of base excision repair players, these generate different dna lesions of abasic sites of strand breaks; We used microarrays to detail the global programme of gene expression underlying the DNA damage response in yeast Experiment Overall Design: Yeaststrains with different expression levels of players in base excision repair (in biological triplicate) were grown to mid log phase. The expression responses were compared to each other and we have deciphered a gene expression profile that is specific for DNA damage in yeast.

2008-06-16 | E-GEOD-9295 | biostudies-arrayexpress

Lamin A/C promotes DNA base excision repair

Project description:Lamin A/C promotes DNA base excision repair

| PRJNA512097 | ENA

RSC chromatin remodeler regulates base excision repair of MMS induced DNA damage

Project description: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. Our data indicate that SWI/SNF is not generally required for NER, but instead promotes repair of CPD lesions at specific yeast genes. In contrast, mutation or depletion of RSC subunits causes a general defect in NER across the yeast genome. Our data indicate that RSC is required for repair not only in nucleosomal DNA, but also neighboring linker DNA and nucleosome-free regions (NFRs). Intriguingly, while depletion of the RSC catalytic subunit also affects base excision repair (BER) of N-methylpurine (NMP) lesions, RSC activity is less important for BER in linker DNA and NFRs. Furthermore, our data indicate that RSC plays a direct role in transcription coupled-NER (TC-NER) of transcribed DNA. These findings help to define the specific genomic and chromatin contexts in which each chromatin remodeler functions in DNA repair, and indicate that RSC plays a unique function in facilitating repair by both NER subpathways.

2021-04-12 | GSE161929 | GEO

RSC chromatin remodeler regulates base excision repair of MMS induced DNA damage

Project description:RSC chromatin remodeler regulates base excision repair of MMS induced DNA damage

| PRJNA679837 | ENA

Acetylation of p62 regulates base excision repair through interaction with APE1

Project description:p62, a well-known adaptor of autophagy, plays multiple functions in response to various stresses. Here, we report a function for p62 in base excision repair that is distinct from its known functions. Loss of p62 impairs BER capacity and increases the sensitivity of cancer cells to alkylating and oxidizing agents. In response to alkylative and oxidative damage, p62 is accumulated in the nucleus，acetylated by hMOF， deacetylated by SIRT7, and acetylated p62 is recruited to chromatin. The chromatin-enriched p62 directly interacts with APE1, a key enzyme of the BER pathway, and promotes its endonuclease activity, which facilitates BER and cell survival. Collectively, our findings demonstrate that p62 is a regulator of BER, and provide further rationale for targeting p62 as a cancer therapeutic strategy.

2022-07-19 | PXD034901 | Pride

Acetylation of p62 regulates base excision repair through interaction with APE1

2022-07-19 | PXD034899 | Pride

Lamin A/C promotes DNA base excision repair (mouse arrays)

Project description:Lamin A/C promotes DNA base excision repair (mouse arrays)

| PRJNA492926 | ENA

Lamin A/C promotes DNA base excision repair (human arrays)

Project description:Lamin A/C promotes DNA base excision repair (human arrays)

| PRJNA512096 | ENA