Chromosome lagging

Amon 1999). In most, but not all eukaryotic cells, unaligned or lagging chromosomes transmit a signal via the protein Mad2, which inhibits the APC and its activator protein Cdc20 and thereby prevents the proteolysis of both 13-type cyclins and securins. It is the block to securin destruction that prevents Sccl cleavage and thereby sister chromatid separation (Fig. 5) (Alexandru et al 1999). 

Erythroblasts in bone marrow undergo a final chromosome replication after which they divide and differentiate into PCEs. Chromosomal breaks or interference in the mitotic process that result in the lagging chromosomes during this division lead to the formation of micronuclei that are similar in appearance but much smaller than the nucleus in immature, nucleated erythrocytes. During differentiation, only the nucleus is expelled from the nucleated erythrocyte, leaving behind any micronuclei formed. 

Bleomycin induced chromosomal damage in Chinese hamster bone marrow gives rise to micronuclei by means of lagging chromatin main and micronuclei eventually become asynchronous in consecutive cell cycles and mitosing main nuclei induce premature chromosome condensation in the micronuclei (Kurten and Obe, 1975). 

The test is used for the detection of cytogenetic damage to the chromosomes or the mitotic apparatus of erythroblasts by analysis of erythrocytes for formation of micronuclei (small nuclei, separate from and additional to the main nuclei of cells, produced during the telophase of mitosis (meiosis) by lagging chromosome fragments or whole chromosomes). When a bone marrow erythroblast develops into a polychromatic erythrocyte (immature erythrocyte), the main nucleus is extruded any micronucleus that has been formed may remain behind in the otherwise anucleated cytoplasm. 

The chromosomes become shorter at each round of DNA replication after removal of the RNA primer from the lagging strand. 

Like bacteria, eukaryotes have several types of DNA polymerases. Some have been linked to particular functions, such as the replication of mitochondrial DNA. The replication of nuclear chromosomes involves DNA polymerase a, in association with DNA polymerase S. DNA polymerase a is typically a multisubunit enzyme with similar structure and properties in all eukaryotic cells. One subunit has a primase activity, and the largest subunit (Afr -180,000) contains the polymerization activity. However, this polymerase has no proofreading 3 —>5 exonuclease activity, making it unsuitable for high-fidelity DNA replication. DNA polymerase a is believed to function only in the synthesis of short primers (containing either RNA or DNA) for Okazaki fragments on the lagging strand. These primers... 

Eukaryotic cells face a special problem in replicating the ends o1 I their linear DNA molecules. Following removal of the RNA primei I from the extreme 5 -end of the lagging strand, there is no way to fill I in the remaining gap with DNA. To solve this problem, and to protea I the ends of the chromosomes from attack by nucleases, noncoding I sequences of DNA complexed with proteins are found at these ... 

Many proteins are required for DNA synthesis and chromosomal replication. These include polymerases helicases, which unwind the parental duplex enzymes that fill in the gaps and join the ends in the case of lagging-strand synthesis enzymes that synthesize RNA primers at various points along the DNA tem-... 

Upstream and downstream genes adjacent to the Corby lag-1 gene correspond to ORF 2 and ORF 3 on the 32.6 kb LPS biosynthesis locus described in strain OLDA52 (Fig. 9). The lag-1 gene is found at various chromosomal locations in different Pontiac-group isolates,53 which suggested that lag-1 may be contained in an unstable genetic element. 

The replication of a linear DNA molecule in a eukaryotic chromosome creates a problem that does not exist for the replication of bacterial circular DNA molecules. The normal mechanism of DNA synthesis (see above) means that the 3 end of the lagging strand is not replicated. This creates a gap at the end of the chromosome and therefore a shortening of the double-stranded replicated portion. The effect is that the chromosomal DNA would become shorter and shorter after each replication. Various mechanisms have evolved to solve this problem. In many organisms the solution is to use an enzyme called telom-erase to replicate the chromosome ends (telomeres). 

MICRONUCLEUS A nucleus, separate from and additional to the main nucleus of a cell, produced during telophase of mitosis or meiosis by lagging chromosomes or chromosomal fragments derived from spontaneous or experimentally induced chromosomal structural changes the smaller of the two nuclei that occur in the cells of ciliate protozoans. 

Micronuclei Small particles of genetic material and consisting of accentric fragments of chromosomes or the entire chromosome that lag behind at anaphase phase of cell division after telophase, the fragments may not be included in the nuclei of daughter cells, but form single or multinuclei in the cytoplasm. 

A multienzyme complex simultaneously carries out both leading and lagging strand replication. You can see the best model of the process in the next figure the lagging strand may curl around so it presents the correct face to the enzyme. The two replication forks proceed around the chromosome, until they meet at the terminus. Termination is poorly defined biochemically, but it is known to require some form of DNA gyrase activity. See Figure 8-12. 

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