The centromere is a constricted region of a chromosome where the kinetochore assembles and sister chromatids are paired. Centromeres contain DNA sequences that bind proteins required for kinetochore assembly. Studies in budding yeast identified a 125 bp centromere DNA sequence containing three conserved elements that assemble a point centromere binding a single microtubule. Fission yeast and higher eukaryotes have regional centromeres formed from arrays of repeated sequences that bind multiple microtubules. The human centromere contains a highly repeated 171bp alpha satellite DNA array ranging from 200kb to 9000kb with some repeats containing a CENP-B box protein binding site.
The centromere is a constricted region of a chromosome where the kinetochore assembles and sister chromatids are paired. Centromeres contain DNA sequences that bind proteins required for kinetochore assembly. Studies in budding yeast identified a 125 bp centromere DNA sequence containing three conserved elements that assemble a point centromere binding a single microtubule. Fission yeast and higher eukaryotes have regional centromeres formed from arrays of repeated sequences that bind multiple microtubules. The human centromere contains a highly repeated 171bp alpha satellite DNA array ranging from 200kb to 9000kb with some repeats containing a CENP-B box protein binding site.
The centromere is a constricted region of a chromosome where the kinetochore assembles and sister chromatids are paired. Centromeres contain DNA sequences that bind proteins required for kinetochore assembly. Studies in budding yeast identified a 125 bp centromere DNA sequence containing three conserved elements that assemble a point centromere binding a single microtubule. Fission yeast and higher eukaryotes have regional centromeres formed from arrays of repeated sequences that bind multiple microtubules. The human centromere contains a highly repeated 171bp alpha satellite DNA array ranging from 200kb to 9000kb with some repeats containing a CENP-B box protein binding site.
The centromere is a waist-like structure or primary constriction of a eukaryotic chromosome
where the kinetochore is assembled and sister chromatids are most intimately paired. Each linear chromosome has particular DNA sequences called CEN sequences, that specify protein-binding sites required for assembly of the kinetochore. Most of our knowledge of the genetics of centromeres has come from work in budding yeast (Saccharomyces cerevisiae). After sequencing the centromeres of all of the 16 yeast chromosomes, investigators concluded that the yeast centromere DNA is about 125 bp long with three conserved sequence elements. These are designated (in the 5 to 3 direction) CDE I (centromere DNA element I, 8 bp), CDE II (78 to 86 bp), and CDE III (25bp). CDE II is extremely (91-95%) AT-rich. CDE III has two different inverted repeats. Recent data indicate that this centromere region may contain a single, modified nucleosome. This type of centromere, in which the kinetochore is assembled as a result of protein recognition of specific DNA sequences, is known as a point centromere. Kinetochores assembled on point centromeres bind single microtubules. Fission yeast (Schizosaccharomyces pombe) centromeres are much more complex than are their counterparts from budding yeast, containing a central core of unique-sequence DNA that is 4-7 kb long, flanked by complex arrays of repeated sequences. This type of centromere, where the kinetochore is assembled on a variable array of repeated DNA sequences, is known as a regional centromere. Kinetochores assembled on regional centromeres bind multiple microtubules (2 to 4 in case of S. pombe). Centromeres of all higher eukaryotes are also regional centromeres. Human centromere DNA has a hierarchic organization. A 171 bp sequence is repeated with slight nucleotide sequence variations to form a higher repeat, which is in turn repeated with high sequence conservation to form a still higher order of repeat called an satellite DNA array or alphoid DNA, which ranges in size from 200 to 9000 kb. Some of the monomeric 171bp blocks have a conserved 17-bp sequence (the CENP-B box), which forms the binding site for the centromeric protein CENP-B. The centromere contains a specialized form of chromatin that is assembled by packing the DNA with histones and other proteins. The nonhistone proteins can be divided into two groups, constitutive and passenger proteins. Constitutive proteins remain associated with the centromere throughout the entire cell life cycle, whereas passenger proteins associate with the centromere during one stage of the life cycle but not others. Other constitutive and passenger proteins assemble to form the microtubule attachment site called the kinetochore. Centromeric chromatin has a histone H3 variant known as CENP-A (centromere protein A) that combines with the other histones to form a new type of nucleosome that is dispersed among normal nucleosomes in the centromere. Centromeres appear to serve two important functions in the cell. First, they are sites at which the kinetochores are assembled. Second, they are essential in keeping the sister chromatids together during mitosis and meiosis. The sister chromatids are held together by multisubunit protein complexes called cohesins. This cohesion between sister chromatids is crucial to the chromosome segregation process and is broken only late in mitosis (at the start of anaphase) to allow the sister chromatids to be pulled apart.