Human RAP1 inhibits non-homologous end joining at telomeres Export

@article{citeulike:5817696, abstract = {Telomeres, the nucleoprotein structures at the ends of linear chromosomes, promote genome stability by distinguishing chromosome termini from DNA double-strand breaks (DSBs). Cells possess two principal pathways for DSB repair: homologous recombination and non-homologous end joining (NHEJ). Several studies have implicated TRF2 in the protection of telomeres from NHEJ, but the underlying mechanism remains poorly understood. Here, we show that TRF2 inhibits NHEJ, in part, by recruiting human RAP1 to telomeres. Heterologous targeting of hRAP1 to telomeric DNA was sufficient to bypass the need for TRF2 in protecting telomeric DNA from NHEJ in vitro. On expanding these studies in cells, we find that recruitment of hRAP1 to telomeres prevents chromosome fusions caused by the loss of TRF2/hRAP1 from chromosome ends despite activation of a DNA damage response. These results provide the first evidence that hRAP1 inhibits NHEJ at mammalian telomeres and identify hRAP1 as a mediator of genome stability.}, author = {Sarthy, Jay and Bae, Nancy S. and Scrafford, Jonathan and Baumann, Peter}, citeulike-article-id = {5817696}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/emboj.2009.275}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/emboj2009275a}, day = {17}, doi = {10.1038/emboj.2009.275}, issn = {0261-4189}, journal = {The EMBO Journal}, keywords = {dna, structure, telomere}, month = {September}, number = {21}, pages = {3390--3399}, posted-at = {2009-11-05 20:21:19}, priority = {2}, publisher = {Nature Publishing Group}, title = {Human RAP1 inhibits non-homologous end joining at telomeres}, url = {http://dx.doi.org/10.1038/emboj.2009.275}, volume = {28}, year = {2009} }

TY - JOUR ID - citeulike:5817696 L3 - citeulike-article-id:5817696 N2 - Telomeres, the nucleoprotein structures at the ends of linear chromosomes, promote genome stability by distinguishing chromosome termini from DNA double-strand breaks (DSBs). Cells possess two principal pathways for DSB repair: homologous recombination and non-homologous end joining (NHEJ). Several studies have implicated TRF2 in the protection of telomeres from NHEJ, but the underlying mechanism remains poorly understood. Here, we show that TRF2 inhibits NHEJ, in part, by recruiting human RAP1 to telomeres. Heterologous targeting of hRAP1 to telomeric DNA was sufficient to bypass the need for TRF2 in protecting telomeric DNA from NHEJ in vitro. On expanding these studies in cells, we find that recruitment of hRAP1 to telomeres prevents chromosome fusions caused by the loss of TRF2/hRAP1 from chromosome ends despite activation of a DNA damage response. These results provide the first evidence that hRAP1 inhibits NHEJ at mammalian telomeres and identify hRAP1 as a mediator of genome stability. IS - 21 JF - The EMBO Journal SN - 0261-4189 EP - 3399 TI - Human RAP1 inhibits non-homologous end joining at telomeres PB - Nature Publishing Group VL - 28 SP - 3390 KW - dna KW - structure KW - telomere AU - Sarthy, Jay AU - Bae, Nancy AU - Scrafford, Jonathan AU - Baumann, Peter PY - 2009/09/17/ UR - http://dx.doi.org/10.1038/emboj.2009.275 ER -