The role of BRCA2 in the fragility of interstitial telomeric sites.

Mutat Res Genet Toxicol Environ Mutagen

Department of Life Sciences, College of Health, Medicine and Life Sciences, Brunel University London, Kingston Lane, Uxbridge UB8 3PH, UK. Electronic address:

Published: June 2022

AI Article Synopsis

  • We studied how radiation affects chromosome structure and DNA damage in both interphase and metaphase cells from Chinese hamster cells with BRCA2 defects compared to control cells.
  • Our methods involved advanced techniques like FISH and TIF to analyze DNA integrity and telomere functions.
  • Results showed that BRCA2-deficient cells had higher levels of DNA damage at both interstitial and terminal telomeric sites, indicating that BRCA2 plays a crucial role in maintaining telomere stability.

Article Abstract

We examined frequencies of radiation-induced chromosomal aberrations, using classical cytological methods, and DNA damage in interphase and metaphase cells, using a combination of FISH, CO-FISH, TIF (telomere dysfunction induced assay) and simultaneous detection of DNA damage and telomeric sequences in metaphase chromosomes, in Chinese hamster cells defective in BRCA2 and control cells. Given that the Chinese hamster genome contains large blocks of interstitial telomeric sites, our results allow us to examine the role of BRCA2 in the potential fragility of these sites, but also whether BRCA2 affects DNA repair within terminal telomeric sequences. BRCA2 defective cells exhibited greater frequencies of DNA damage within interstitial telomeric sites, as well as within terminal telomeric sites, relative to control cells. Therefore, BRCA2 deficiency contributes to the telomere dysfunction phenotype in Chinese hamster cells.

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http://dx.doi.org/10.1016/j.mrgentox.2022.503476DOI Listing

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