DNA damage response at functional and dysfunctional telomeres

DNA damage response at functional and dysfunctional telomeres.

The ends of eukaryotic chromosomes have long been defined as structures that must avoid being detected as DNA breaks. They are protected from checkpoints, homologous recombination, end-to-end fusions, or other events that normally promote repair of intrachromosomal DNA breaks. This differentiation is thought to be the consequence of a unique organization of chromosomal ends into specialized nuc...

DNA Damage Foci at Dysfunctional Telomeres

We report cytologic and genetic data indicating that telomere dysfunction induces a DNA damage response in mammalian cells. Dysfunctional, uncapped telomeres, created through inhibition of TRF2, became associated with DNA damage response factors, such as 53BP1, gamma-H2AX, Rad17, ATM, and Mre11. We refer to the domain of telomere-associated DNA damage factors as a Telomere Dysfunction-Induced F...

Corrigendum: DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs

DNA damage response inhibition at dysfunctional telomeres by modulation of telomeric DNA damage response RNAs

The DNA damage response (DDR) is a set of cellular events that follows the generation of DNA damage. Recently, site-specific small non-coding RNAs, also termed DNA damage response RNAs (DDRNAs), have been shown to play a role in DDR signalling and DNA repair. Dysfunctional telomeres activate DDR in ageing, cancer and an increasing number of identified pathological conditions. Here we show that,...

BRCA1 in the DNA damage response and at telomeres

Mutations of the breast and ovarian cancer susceptibility gene 1 (BRCA1) account for about 40-45% of hereditary breast cancer cases. Moreover, a significant fraction of sporadic (non-hereditary) breast and ovarian cancers exhibit reduced or absent expression of the BRCA1 protein, suggesting an additional role for BRCA1 in sporadic cancers. BRCA1 follows the classic pattern of a highly penetrant...