Virgin J B, Metzger J, Smith G R
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, USA.
Genetics. 1995 Sep;141(1):33-48. doi: 10.1093/genetics/141.1.33.
The ade6-M26 mutation of the fission yeast Schizosaccharomyces pombe creates a meiotic recombination hotspot that elevates ade6 intragenic recombination approximately 10-15-fold. A heptanucleotide sequence including the M26 point mutation is required but not sufficient for hotspot activity. We studied the effects of plasmid and chromosomal context on M26 hotspot activity. The M26 hotspot was inactive on a multicopy plasmid containing M26 embedded within 3.0 or 5.9 kb of ade6 DNA. Random S. pombe genomic fragments totaling approximately 7 Mb did not activate the M26 hotspot on a plasmid. M26 hotspot activity was maintained when 3.0-, 4.4-, and 5.9-kb ade6-M26 DNA fragments, with various amounts of non-S. pombe plasmid DNA, were integrated at the ura4 chromosomal locus, but only in certain configurations relative to the ura4 gene and the cointegrated plasmid DNA. Several integrations created new M26-independent recombination hotspots. In all cases the non-ade6 DNA was located > 1 kb from the M26 site, and in some cases > 2 kb. Because the chromosomal context effect was transmitted over large distances, and did not appear to be mediated by a single discrete DNA sequence element, we infer that the local chromatin structure has a pronounced effect on M26 hotspot activity.
粟酒裂殖酵母(Schizosaccharomyces pombe)的ade6-M26突变产生了一个减数分裂重组热点,使ade6基因内重组提高了约10至15倍。一个包含M26点突变的七核苷酸序列是热点活性所必需的,但并不充分。我们研究了质粒和染色体背景对M26热点活性的影响。M26热点在含有嵌入3.0或5.9 kb ade6 DNA内的M26的多拷贝质粒上无活性。总计约7 Mb的随机粟酒裂殖酵母基因组片段在质粒上未激活M26热点。当带有不同量非粟酒裂殖酵母质粒DNA的3.0 kb、4.4 kb和5.9 kb ade6-M26 DNA片段整合到ura4染色体位点时,M26热点活性得以维持,但仅在相对于ura4基因和共整合质粒DNA的某些构型中如此。几次整合产生了新的不依赖M26的重组热点。在所有情况下,非ade6 DNA位于距M26位点>1 kb处,在某些情况下>2 kb。由于染色体背景效应能在远距离传递,且似乎不是由单个离散的DNA序列元件介导的,我们推断局部染色质结构对M26热点活性有显著影响。