McGinn Jon, Marraffini Luciano A
Laboratory of Bacteriology, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Bacteriology, The Rockefeller University, New York, NY 10065, USA.
Mol Cell. 2016 Nov 3;64(3):616-623. doi: 10.1016/j.molcel.2016.08.038. Epub 2016 Sep 8.
CRISPR-Cas systems defend prokaryotes against viruses and plasmids. Short DNA segments of the invader, known as spacers, are stored in the CRISPR array as immunological memories. New spacers are added invariably to the 5' end of the array; therefore, the first spacer matches the latest foreign threat. Whether this highly polarized order of spacer insertion influences CRISPR-Cas immunity has not been explored. Here we show that a conserved sequence located immediately upstream of the CRISPR array specifies the site of new spacer integration. Mutation of this sequence results in erroneous incorporation of new spacers into the middle of the array. We show that spacers added through polarized acquisition give rise to more robust CRISPR-Cas immunity than spacers added to the middle of the array. This study demonstrates that the CRISPR-Cas system specifies the site of spacer integration to optimize the immune response against the most immediate threat to the host.
CRISPR-Cas系统保护原核生物免受病毒和质粒的侵害。入侵者的短DNA片段，即间隔序列，作为免疫记忆存储在CRISPR阵列中。新的间隔序列总是添加到阵列的5'端；因此，第一个间隔序列与最新的外来威胁相匹配。间隔序列插入的这种高度极化顺序是否影响CRISPR-Cas免疫尚未得到探索。在这里，我们表明位于CRISPR阵列紧邻上游的保守序列指定了新间隔序列整合的位点。该序列的突变导致新的间隔序列错误地掺入阵列中间。我们表明，通过极化获得添加的间隔序列比添加到阵列中间的间隔序列产生更强的CRISPR-Cas免疫。这项研究表明，CRISPR-Cas系统指定间隔序列整合的位点，以优化针对宿主最直接威胁的免疫反应。
