Stavenhagen J B, Zakian V A
Princeton University, Department of Molecular Biology, Princeton, New Jersey 08544-1014, USA.
Genes Dev. 1998 Oct 1;12(19):3044-58. doi: 10.1101/gad.12.19.3044.
In Saccharomyces cerevisiae, proximity to a telomere affects both transcription and replication of adjacent DNA. In this study, we show that telomeres also impose a position effect on mitotic recombination. The rate of recombination between directly repeated tracts of telomeric C1-3A/TG1-3 DNA was reduced severely by proximity to a telomere. In contrast, recombination of two control substrates was not affected by telomere proximity. Thus, unlike position effects on transcription or replication, inhibition of recombination was sequence specific. Moreover, the repression of recombination was not under the same control as transcriptional repression (telomere position effect; TPE), as mutations in genes essential for TPE did not alleviate telomeric repression of recombination. The reduction in recombination between C1-3A/TG1-3 tracts near the telomere was caused by an absence of Rad52p-dependent events as well as a reduction in Rad1p-dependent events. The sequence-specific repression of recombination near the telomere was eliminated in cells that overexpressed the telomere-binding protein Rap1p, a condition that also increased recombination between C1-3A/TG1-3 tracts at internal positions on the chromosome. We propose that the specific inhibition between C1-3A/TG1-3 tracts near the telomere occurs through the action of a telomere-specific end-binding protein that binds to the single-strand TG1-3 tail generated during the processing of recombination intermediates. The recombination inhibitor protein may also block recombination between endogenous telomeres.
在酿酒酵母中,靠近端粒会影响相邻DNA的转录和复制。在本研究中,我们表明端粒也对有丝分裂重组施加位置效应。端粒C1-3A/TG1-3 DNA的直接重复序列之间的重组率因靠近端粒而严重降低。相比之下,两种对照底物的重组不受端粒靠近的影响。因此,与对转录或复制的位置效应不同,重组抑制是序列特异性的。此外,重组的抑制与转录抑制(端粒位置效应;TPE)不受相同的调控,因为TPE所必需的基因中的突变并未减轻端粒对重组的抑制。端粒附近C1-3A/TG1-3序列之间重组的减少是由于缺乏Rad52p依赖性事件以及Rad1p依赖性事件的减少所致。在过表达端粒结合蛋白Rap1p的细胞中,端粒附近重组的序列特异性抑制被消除,这种情况也增加了染色体内部位置的C1-3A/TG1-3序列之间的重组。我们提出,端粒附近C1-3A/TG1-3序列之间的特异性抑制是通过一种端粒特异性末端结合蛋白的作用发生的,该蛋白与重组中间体加工过程中产生的单链TG1-3尾巴结合。重组抑制蛋白也可能阻断内源性端粒之间的重组。