DNA Replication

James Watson and Francis Crick (1953 a,b) proposed that the genetic material is in the form of a double helix. This structure has many functional implications. For example, it automatically explains how genetic information is passed from one generation to another. Because the two DNA strands are complementary, they can be separated and rebuilt to form duplicate helices (11:115-140).

Mammalian cells contain approximately 2 meters of DNA fiber. This genomic material is connected to a subnuclear proteinaceous matrix. Its periodic attachment to this scaffold forms a series of loops (3:85-111).

Most eukaryotic cells replicate all of their genes during a specific period of the cell cycle. This synthesis, or S, phase is preceded by a G1 phase and followed by a G2 phase. G1 is the gap between the end of mitosis (i.e., M phase) and the beginning of S phase, and G2 is the interval separating the end of S phase and the beginning of M phase (10:141-171).

Normal cells process a number of different environmental signals during the G1 phase. These signals indicate whether or not conditions are right for DNA synthesis. Thus, the G1 to S phase transition marks a principal point of DNA replication regulation. In y

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eplicators often contain short palindromes (i.e., A/T-rich regions). In addition, they may also contain a variable number of simple repeating sequences clustered within a fairly short distance. The initiation of nascent strands usually occurs within a few hundred base pairs of these sequences. The replicator and the nascent strand start sites together form the replicon's origin (3:85-111). In mammalian chromosomes, a replicon may include any "stretch of DNA synthesized by two diverging forks (3:85-111)." Thus, initiation in mammalian chromosomes is bidirectional. When gently spread chromatin is observed through an electron microscope, the replicating structures look like small bubbles, or eyes. One of the must thoroughly studied replication origins occurs in S. cerevisiae. Because of their ability to confer autonomous replication on plasmids, yeast origins are known as autonomous replicating sequences (ARS). They consist of two domains, A and B. Domain A consists of the following: 5'(A/T)TTTA(T/C)(A/G)TTT(A/T)3'. In contrast, domain B consists of two to three partially redundant subdomains with little or no sequence conservation. The ARS domains are recognized by a multiunit initiator protein complex, Orc1-6 (12:414-4
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Approximate Word count = 2188
Approximate Pages = 9 (250 words per page)

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