Baker R E, Harris K, Zhang K
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Genetics. 1998 May;149(1):73-85. doi: 10.1093/genetics/149.1.73.
CP1 (encoded by CEP1) is a Saccharomyces cerevisiae chromatin protein that binds a DNA element conserved in centromeres and in the 5'-flanking DNA of methionine biosynthetic (MET) genes. Strains lacking CP1 are defective in chromosome segregation and MET gene transcription, leading to the hypothesis that CP1 plays a general role in assembling higher order chromatin structures at genomic sites where it is bound. A screen for mutations synthetically lethal with a cep1 null allele yielded five recessive csl (cep1 synthetic lethal) mutations, each defining a unique complementation group. Four of the five mutations synergistically increased the loss rate of marker chromosomes carrying a centromere lacking the CP1 binding site, suggesting that the cep1 synthetic lethality was due to chromosome segregation defects. Three of these four CSL genes were subsequently found to be known or imputed kinetochore genes: CEP3, NDC10, and CSE4. The fourth, CSL4, corresponded to ORF YNL232w on chromosome XIV, and was found to be essential. A human cDNA was identified that encoded a protein homologous to Csl4 and that complemented the csl4-1 mutation. The results are consistent with the view that the major cellular role of CP1 is to safeguard the biochemical integrity of the kinetochore.
CP1（由CEP1编码）是一种酿酒酵母染色质蛋白，它能结合在着丝粒和甲硫氨酸生物合成（MET）基因的5'侧翼DNA中保守的DNA元件。缺乏CP1的菌株在染色体分离和MET基因转录方面存在缺陷，这导致了一种假设，即CP1在其结合的基因组位点组装高阶染色质结构中发挥普遍作用。对与cep1无效等位基因合成致死的突变进行筛选，得到了五个隐性csl（cep1合成致死）突变，每个突变定义了一个独特的互补群。五个突变中的四个协同增加了携带缺乏CP1结合位点的着丝粒的标记染色体的丢失率，这表明cep1合成致死是由于染色体分离缺陷。随后发现这四个CSL基因中的三个是已知的或推测的动粒基因：CEP3、NDC10和CSE4。第四个基因CSL4对应于第十四号染色体上的开放阅读框YNL232w，并且被发现是必需的。鉴定出了一个人类cDNA，它编码与Csl4同源的蛋白质，并能互补csl4-1突变。这些结果与CP1的主要细胞作用是维护动粒的生化完整性这一观点一致。
