Mimitou Eleni P, Yamada Shintaro, Keeney Scott
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Science. 2017 Jan 6;355(6320):40-45. doi: 10.1126/science.aak9704.
DNA double-strand breaks that initiate meiotic recombination are exonucleolytically processed. This 5'→3' resection is a central, conserved feature of recombination but remains poorly understood. To address this lack, we mapped resection endpoints genome-wide at high resolution in Saccharomyces cerevisiae Full-length resection requires Exo1 exonuclease and the DSB-responsive kinase Tel1, but not Sgs1 helicase. Tel1 also promotes efficient and timely resection initiation. Resection endpoints display pronounced heterogeneity between genomic loci that reflects a tendency for nucleosomes to block Exo1, yet Exo1 also appears to digest chromatin with high processivity and at rates similar to naked DNA in vitro. This paradox points to nucleosome destabilization or eviction as a defining feature of the meiotic resection landscape.
引发减数分裂重组的DNA双链断裂会被核酸外切酶处理。这种5'→3'切除是重组的核心保守特征，但仍知之甚少。为了解决这一不足，我们在酿酒酵母中以高分辨率全基因组范围内绘制了切除终点图谱。全长切除需要Exo1核酸外切酶和DSB反应激酶Tel1，但不需要Sgs1解旋酶。Tel1还促进高效及时的切除起始。切除终点在基因组位点之间表现出明显的异质性，这反映了核小体阻碍Exo1的倾向，然而Exo1在体外似乎也能以高持续性和与裸露DNA相似的速率消化染色质。这一矛盾表明核小体不稳定或去除是减数分裂切除景观的一个决定性特征。
