Chromosomes replication

DNA in mammalian cells is organized in complex structures called chromosomes (prokaryotes do not have a nucleus, do not divide by mitosis, and do not, strictly speaking, have chromosomes). The DNA in the chromosomes of human and other eukaryotic cells is intimately associated with two classes of proteins called histones and nonhistones. Collectively, DNA, histones, and nonhistones constitute chromatin, from which the name chromosome is derived. The DNA in a chromosome is an extremely long, linear molecule that must be condensed and organized to fit into the chromosomes in the nucleus. (The DNA in the 46 human chromosomes would be about 1 m long if fully extended.) Histones are responsible for the structural organization of DNA in chromosomes the nonhistone proteins 

Structure of a nucleosome. DNA is looped around a core of eight histone proteins (pairs of four different histone proteins) and connected to adjacent nucleosomes by linker DNA and another histone (HI). 

Histones share a similar primary structure among eukaryotic species. However, they undergo various posttransla-tional modifications such as phosphorylation, acetylation, methylation, and ADP ribosylation.The chemical modifications of histones can alter their net charge, shape, and other properties affecting DNA binding. 

Hypothetical stages in the condensation of DNA with chromatin to form a chromosome, (a) Double-stranded DNA. (b)-(e) Formation of nucleosome beads and fibers consisting of histones and condensed DNA to form (f) a metaphase chromosome. These proposed intermediates are derived from dissociation reactions with intact chromosomes. 

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Introduction 4.1 The basis for selective inhibition of chromosome replication and... 

The basic sequence of events for microbial chromosome replication is as follows. 

Since nucleic acids and enzymes play such a large role in chromosome replication during mitosis, a considerable amount of research has been conducted in this area to control viruses. On the molecular level, analogues of nucleic acids are capable of forming complexes with adenine, cytosine, uracil, thymine, and guanine. Through complexation, these nucleic acid analogues are potential inhibitors of biosyntheses that require nucleic acids as templates. 

Enoch, T., and Nurse, P. (1991). Coupling M phase and S phase controls maintaining the dependence of mitosis on chromosome replication. Cell 65 921-923. 

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. 

O. Hyrien, and M. Mechali, Chromosomal replication initiates and terminates at random sequences but at regular intervals in the ribosomal DNA of Xenopus early embryos. EMBO J. 12, 4511 520 (1993). 

Complete Chromosome Replication Can Require Site-Specific Recombination... 

Katayama, T. (2001) Feedback controls restrain the initiation of Escherichia coli chromosomal replication. Mol. Microbiol. 41, 9-17. 

Replication of the Escherichia coli Chromosome Initiation and Termination of Escherichia coli Chromosomal Replication DNA Replication in Eukaryotic Cells Eukaryotic Chromosomal DNA SV40 Is Similar to Its Host in Its Mode of Replication... 

Initiation and Termination of Escherichia coli Chromosomal Replication... 

Two aspects of E. coli chromosomal replication still to be considered are initiation and termination. From what has been said we conjecture that replication initiates at a unique site, proceeds bidirectionally, and terminates at a point where the two oppositely advancing growth forks meet. To study initiation it was first necessary to isolate that segment... 

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-... 

Enzymes that catalyze the synthesis of DNA using an RNA template are known as reverse transcriptases. The first reverse transcriptase discovered was encoded by an RNA retrovirus. This enzyme is needed in the virus replication cycle. Some animal viruses pass through an RNA intermediate and also require a reverse transcriptase to replicate the viral DNA. Similarly, a number of transposable elements found in cellular chromosomes replicate through RNA intermediates they usually encode a reverse transcriptase. A unique reverse transcriptase called telomerase is used to synthesize the DNA at the ends of linear eukaryotic chromosomes. 

Newlin, C. S., Yeast chromosome replication and segregation. Microbiol. Rev. 52 568-601, 1988. 

Bacterial family C polymerases are the major chromosomal replicative enzyme (Kornberg and Baker, 1992). Like other replicative polymerases, the holoenzyme interacts with other proteins and forms a large multisubunit complex consisting of at least 10 subunits (Kornberg and Baker, 1992). The a-subunit contains the DNA polymerase activity that is tightly associated with the e-subunit, which contains a 3 -5 exonuclease activity (Kelman and O Donnell, 1995). 

Fig. 2. Replication of the bacterial circular chromosome. Replication starts from a single origin and proceeds bi-directionally (a) moving around the chromosome with time (b). The two replication forks eventually meet and fuse. The two circular daughter DNA molecules produced each have one original template DNA strand (thin line) and one new strand (thick line).

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