Leading strand, DNA

LDA, see Lithium diisopropylamide LDL, heart disease and, 1090-1091 Le Bel, Joseph Achille, 7-8 Leading strand, DNA replication and, 1107... 

Leading strand (Section 28.10) In DNA replication, the strand that grows toward the replication fork. 

The biological activity of calicheamicin 4 (simplified structure) is based on the ability to damage DNA. At the reaction site, initially the distance between the triple bonds is diminished by an addition reaction of a sulfur nucleophile to the enone carbon-carbon double bond, whereupon the Bergman cyclization takes place leading to the benzenoid diradical 5, which is capable of cleaving double-stranded DNA." ... 

Registiy of Mass Spectral Data, 412 Replication (DNA). 1106-1107 direction of, 1107 error rate during. 1107 lagging strand in, 1107 leading strand in, 1107 Okazaki fragments in, 1107 replication fork in, 1107 Replication fork (DNA), 1107 Reserpine, structure of, 65 Residue (protein), 1027 Resist, photolithography and, 505-506... 

Depurination - N7 alkylation may cause cleavage of the imidazole ring and excision of the guanine residue, leading to DNA strand breakage. 

The multiprotein unit that synthesize RNA by copying the sequence information from the leading strand of the DNA. Its activity is tightly controlled by phosphorylation of the C-termal domain (CTD), access to DNA and interaction by general and sequence specific transcription factors and coactivators and corepressors. 

Each strand of the double helix is replicated simultaneously but by somewhat different mechanisms. A complex of proteins, including DNA polymerase, replicates the leading strand continuously in the 5 to 3 direction. The lagging strand is replicated discon-tinuously, in short pieces of 150-250 nucleotides, in the 3 to 5 direction. 

DNA, apsPtDNA, contains an overhanging G-residue that undergoes preferential inter-duplex crosslinking (4°C over a period of 2 months) to form 3 -crosslinked complementary strands. Duplex melting and intramolecular hybridization at pH 4.2 leads to the formation of parallel stranded DNA, psPtDNA. 

DNA replication differs between the leading strand and the lagging strand of the DNA double helix. In cells, replication Af the lagging strand involves the formation of short RNA primers by action of an enzyme called RNA primase (or primase for short). Such RNA primers are made at intervals on the lagging strand and are then removed and replaced with DNA by DNA polymerase. 

Figure 5.14 Events in the replication of < >X174 DNA. (a) Formation of the replicating double-stranded DNA (RF). (b) Rolling circle replication leads to the formation of virus progeny.

Carboplatin -atypical alkylating agent leading to DNA strand breakage during replication -bone marrow suppression—particularly thrombocytopenia -nausea and vomiting -liver function test abnormalities -uncommon neurotoxicity, ototoxicity... 

In vitro studies of DNA interactions with the reactive ben-zo[a]pyrene epoxide BPDE indicate that physical binding of BPDE occurs rapidly on a millisecond time scale forming a complex that then reacts much more slowly on a time scale of minutes (17). Several reactive events follow formation of the physical complex. The most favorable reaction is the DNA catalyzed hydrolysis of BPDE to the tetrol, BPT (3,5,6,8,17). At 25°C and pH=7.0, the hydrolysis of BPDE to BPT in DNA is as much as 80 times faster than hydrolysis without DNA (8). Other reactions which follow formation of physical complexes include those involving the nucleotide bases and possibly the phosphodiester backbone. These can lead to DNA strand scission (9 34, 54-56) and to the formation of stable BPDE-DNA adducts. Adduct formation occurs at the exocyclic amino groups on the nucleotide bases and at other sites (1,2,9,17,20, 28,33,34,57,58). The pathway which leads to hydrocarbon adducts covalently bound to the 2-amino group of guanine has been the most widely studied. 

After synthesis, the RNA primers must be removed, gaps filled in, and the strands joined to give a linear, duplex DNA. New histones are added to the lagging strand (which is now a duplex) while the old histones remain with the leading strand. As the smoke slowly clears, we have a copy of the original DNA. 

---