DNA replication repair

Yeast RadlSp functions with the RING finger protein RadSp in error-free post-replicative DNA repair. 

Type II topoisomerases are essential and function in replication, DNA repair, transcription, and chromosome segregation at mitosis.345,349 Yeast with a top2 mutation dies during mitosis with hopelessly entangled daughter chromosomes.353 A fluorescent antibody to eukaryotic topoisomerase II binds to chromosomes, probably at the bases of the radial loops... 

The bacterial protein LexA has been identified as playing a key role in the acquisition of bacterial mutations. Repressor LexA represses SOS response genes that code for those DNA-polymerases required for repairing DNA damage. The SOS response is a post-replication DNA-repair system that allows DNA replication to bypass lesions or errors in the DNA. 

DNA can also be a target for alkaloids planar and lipophilic alkaloids, such as berberine and sanguinarine (Figure 1.6) are intercalating compounds that assemble between the stacks of paired nucleotides in the DNA double helix [2,3,18,23]. DNA intercalation can disturb replication, DNA repair, and DNA topoisomerases. Frameshift mutations are one of the adverse consequences of intercalating compounds. Some alkaloids, such as pyrrolizidine alkaloids, aristolochic acids, cycasin, and furoquinoline alkaloids, are known to form covalent adducts with DNA bases. Mutations and tumor formation can be the result of such interactions. DNA alkylation occurs in some alkaloids only after activation by liver enzymes, such as cytochrome p450 oxidases (pyrrolizidine alkaloids, aristolochic acids) [17,18,24]. 

Biological activity Replication DNA repair Replication Replication Replication... 

RPA Replication protein A Inhibition by protein binding Replication/DNA Repair Dutta etal. (1993)... 

Biological function Lagging strand replication DNA repair Mitochondrial DNA replication Leading strand replication Replicadoi... 

Kesti, T., Flick, K., Keranen, S., Syvaoja, J. E., and Wittenberg, C. (1999). DNA polymerase epsilon catalytic domains are dispensable for DNA replication, DNA repair, and cell viabUily. Mol. Cell 3, 679-685. 

The formation of mono-, oligo-, and of linear or branched poly(ADP-ribose) protein conjugates by poly(ADP-ribose) synthetase has been described by various investigators. This protein modification by ADP-ribosylation has been correlated with the biochemical and biological processes of DNA replication, DNA repair, chromatin condensation, regulation of gene expression, and cellular differentiation (for reviews, see [17-19]). While the modification of chromatin constituents, especially of the histones, has been extensively studied, information on the ADP-ribosylation of other subnuclear constituents is scarce [20]. 

Biological data suggest that ADP-ribosylation reactions are involved in all major chromatin functions, i.e., DNA replication, DNA repair, and transcription of genes [2]. Consequently, one can postulate that the target mechanism under ADP-ribosylation control is common to all these chromatin functions [20]. 

The enzymes involved with DNA replication, DNA repair, DNA topo-isomerase, and transcriptiOTi are important targets in all organisms. Inhibitors of these systems are often active against bacteria, fungi, and animal cells. The DNA itself can be modified by compounds with reactive groups, such as epoxides. Interaction between furanocoumarin and DNA occurs in two steps ... 

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