Publications by authors named "K K N Guturi"
Article Synopsis
- Breast cancer with BRCA1/2 mutations often recurs and resists treatments like PARP inhibitors, leading to a search for new targeted therapies.
- Researchers found that losing RNF8 can protect against breast tumors in Brca1-mutant mice, while in human cancer cells, RNF8 deficiency increases DNA damage and leads to cancer cell death through R-loop accumulation.
- The study reveals that RNF8 interacts with XRN2 to resolve R-loops, and its absence disrupts this process, causing genomic instability and highlighting a synthetic lethal relationship between RNF8 and BRCA1.
Germline mutations in BRCA1 and BRCA2 (BRCA1/2) genes considerably increase breast and ovarian cancer risk. Given that tumors with these mutations have elevated genomic instability, they exhibit relative vulnerability to certain chemotherapies and targeted treatments based on poly (ADP-ribose) polymerase (PARP) inhibition. However, the molecular mechanisms that influence cancer risk and therapeutic benefit or resistance remain only partially understood.
View Article and Find Full Text PDFThe E3 ubiquitin ligase RNF8 plays critical roles in maintaining genomic stability by promoting the repair of DNA double-strand breaks (DSBs) through ubiquitin signaling. Abnormal activation of Notch signaling and defective repair of DSBs promote breast cancer risk. Here, we found that low expression of the full-length RNF8 correlated with poor prognosis for breast cancer patients.
View Article and Find Full Text PDFTopoisomerase IIα (TOP2α) is essential for chromosomal condensation and segregation, as well as genomic integrity. Here we report that RNF168, an E3 ligase mutated in the human RIDDLE syndrome, interacts with TOP2α and mediates its ubiquitylation. RNF168 deficiency impairs decatenation activity of TOP2α and promotes mitotic abnormalities and defective chromosomal segregation.
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