2024-03-29T05:43:02Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1215762019-09-27T13:02:12Zcom_10261_134com_10261_1col_10261_387
00925njm 22002777a 4500
dc
Pardo, Benjamín
author
Aguilera, Andrés
author
2012-09-27
DNA double-strand break (DSB) repair occurring in repeated DNA sequences often leads to the generation of chromosomal rearrangements. Homologous recombination normally ensures a faithful repair of DSBs through a mechanism that transfers the genetic information of an intact donor template to the broken molecule. When only one DSB end shares homology to the donor template, conventional gene conversion fails to occur and repair can be channeled to a recombinationdependent replication pathway termed break-induced replication (BIR), which is prone to produce chromosome nonreciprocal translocations (NRTs), a classical feature of numerous human cancers. Using a newly designed substrate for the analysis of DSB–induced chromosomal translocations, we show that Mus81 and Yen1 structure-selective endonucleases
(SSEs) promote BIR, thus causing NRTs. We propose that Mus81 and Yen1 are recruited at the strand invasion intermediate to allow the establishment of a replication fork, which is required to complete BIR. Replication template switching during BIR, a feature of this pathway, engenders complex chromosomal rearrangements when using repeated DNA sequences dispersed over the genome. We demonstrate here that Mus81 and Yen1, together with Slx4, also promote template switching during BIR. Altogether, our study provides evidence for a role of SSEs at multiple steps during BIR, thus participating in the destabilization of the genome by generating complex chromosomal rearrangements.
PLoS Genetics 8(9): e1002979 (2012)
1553-7390
http://hdl.handle.net/10261/121576
10.1371/journal.pgen.1002979
1553-7404
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100002915
http://dx.doi.org/10.13039/501100003043
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100011011
23071463
Complex Chromosomal Rearrangements Mediated by Break-Induced Replication Involve Structure-Selective Endonucleases