Vinay Eapen | Brandeis University (original) (raw)

Papers by Vinay Eapen

Research paper thumbnail of The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end-resection and checkpoint deactivation

… and Cellular Biology, 2012

Research paper thumbnail of DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase

Proceedings of the …, 2013

Research paper thumbnail of DNA damage signaling triggers the cytoplasm-to-vacuole pathway of autophagy to regulate cell cycle progression

Research paper thumbnail of Sgs1 and exo1 redundantly inhibit break-induced replication and de novo telomere addition at broken chromosome ends

PLoS genetics, Jan 1, 2010

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired ... more In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 59 to 39 resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1D exo1D strains, where there is little 59 to 39 resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1D, or exo1D cells. In sgs1D exo1D, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 59 to 39 resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 59 to 39 resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition.

Research paper thumbnail of The Saccharomyces cerevisiae chromatin remodeler Fun30 regulates DNA end-resection and checkpoint deactivation

… and Cellular Biology, 2012

Research paper thumbnail of DNA damage checkpoint triggers autophagy to regulate the initiation of anaphase

Proceedings of the …, 2013

Research paper thumbnail of DNA damage signaling triggers the cytoplasm-to-vacuole pathway of autophagy to regulate cell cycle progression

Research paper thumbnail of Sgs1 and exo1 redundantly inhibit break-induced replication and de novo telomere addition at broken chromosome ends

PLoS genetics, Jan 1, 2010

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired ... more In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 59 to 39 resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1D exo1D strains, where there is little 59 to 39 resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1D, or exo1D cells. In sgs1D exo1D, repair by GC is severely inhibited, but cell viaiblity remains high because of new telomere formation. These data suggest that the extensive 59 to 39 resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 59 to 39 resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition.