Publications by authors named "R Pavani"
DNA lesions that block transcription induce the death of Trypanosoma cruzi via ATR activation, which is dependent on the presence of R-loops.
DNA Repair (Amst)
September 2024
Article Synopsis
- Trypanosoma cruzi, the agent responsible for Chagas disease, exhibits unique biological traits and responds to DNA damage through a specific repair pathway called transcription-coupled nucleotide excision repair (TC-NER).
- When UV light induces DNA lesions, unresolved transcriptional stress can lead to a programmed cell death mechanism that resembles apoptosis.
- The study reveals that the Cockayne Syndrome B protein (CSB) plays a crucial role in this process, as its overexpression increases cell death after UV exposure, while its absence confers resistance, suggesting an ATR-dependent apoptosis-like signaling in T. cruzi.
The outcome of CRISPR-Cas-mediated genome modifications is dependent on DNA double-strand break (DSB) processing and repair pathway choice. Homology-directed repair (HDR) of protein-blocked DSBs requires DNA end resection that is initiated by the endonuclease activity of the MRE11 complex. Using reconstituted reactions, we show that Cas9 breaks are unexpectedly not directly resectable by the MRE11 complex.
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- * Our findings reveal that when there are leading-strand nicks, it can lead to more severe double-strand breaks which, if not quickly fixed, might contribute to cancer.
- * Interestingly, while these breaks don't require the BRCA1 protein for their formation, BRCA1 still plays a role in helping repair processes operate better by managing other repair proteins.
Article Synopsis
- When BRCA1 and BRCA2 genes are mutated, they can't fix DNA breaks properly, which can lead to cancer.
- Scientists found that cells with BRCA1 mutations rely on a factor called EXO1 to fix DNA damage, making EXO1 a weak spot for these cells.
- If EXO1 is missing in BRCA1-mutated cells, they struggle to repair DNA breaks, but BRCA2-mutated cells can still manage without EXO1, suggesting that targeting EXO1 could help treat BRCA1-related cancers.
Deficiency for the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR) leads to chromosomal instability and diseases such as cancer. Yet, defective HR also results in vulnerabilities that can be exploited for targeted therapy. Here, we identify such a vulnerability and show that BRCA1-deficient cells are dependent on the long-range end-resection factor EXO1 for survival.
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