DNA replication initiation

Chaudhuri B, Xu H, Todorov 1, Dutta A, Yates JL (2001) Human DNA replication initiation factors, ORC and MCM, associate with oriP of Epstein-Barr virus. Proc Natl Acad Sci USA 98 10085-10089... 

T. Nenguke, M. I. Aladjem, J. F. Gusella, N. S. Wexler, and N. Arnheim, Candidate DNA replication initiation regions at human trinucleotide repeat disease loci. Hum. Mol. Genet. 12, 1021-1028 (2003). 

C. Girard-Reydet, D. Gregoire, Y. Vassetzky, and M. Mechali, DNA replication initiates at domains overlapping with nuclear matrix attachment regions in the Xenopus and mouse c-myc promoter. Gene 332, 129-138 (2004). 

For S phase to be completed In a timely manner, DNA replication initiates from multiple origins In eukaryotes. In S. cerevisiae, what role do S-phase CDK-cyclIn complexes play to ensure that the entire genome Is replicated once and only once per cell cycle ... 

DNA replication initiates at a unique location on the E. coli origin known as the replication origin. Bidirectional fork movement leads to the complete replication of the chromosome as the two replication forks meet approximately half way around the chromosome. 

Mitochondria - Figure 24.39 illustrates the unusual DNA replication initiation scheme employed by animal cell mitochondria. This involves two unidirectional replication processes. 

Crosslinks result from the reaction of a bifunctional electrophilic species with DNA bases and imply a covalent link between two adjacent DNA strands which inhibits DNA replication. Primary targets within bases are N7 and 06 in guanine and N3 in cytosine. The initial lesions are removed by the suicide enzyme alkyltrans-ferase, whereas nucleotide excision repair is needed for frilly established crosslinks. 

DNA synthesis during S phase of the cell cycle resulting in a doubling of the genomic DNA. Replication can be subdivided into three distinct phases initiation, elongation, and termination. 

The multiple sites that serve as origins for DNA replication in eukaryotes are poorly defined except in a few animal viruses and in yeast. However, it is clear that initiation is regulated both spatially and temporaUy, since clusters of adjacent sites initiate rephcation synchronously. There are suggestions that functional domains of chromatin replicate as intact units, implying that the origins of rephcation are specificaUy located with respect to transcription units. 

Blow, J. J., and Nurse, P. (1990). Acdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts. Cell 62 855-862. 

Our studies of the ERT cell cycles show that they are regulated by nutrition (Britton Edgar 1998). If the newly hatched larva is starved for dietary amino acids, DNA replication in most ERTs is not initiated. Under starvation conditions these tissues express low levels of cyclin E and E2F, the transcription factor which is probably responsible for cyclin E expression. If either E2F or cyclin E is induced in starved larvae, DNA replication in the ERTs is activated, and thus expression of these genes appears to limit the ERT cell cycle. When nutrient-deprived larvae are fed, expression of E2F and cyclin E mRNAs increases approximately sixfold, and DNA replication is initiated in most ERT cells. If the animal is first fed and then starved, the ERT cell cycle is activated and then inactivated quite rapidly. These experiments all indicate that the ERT cell cycle is nutrition-responsive, rather than controlled by a rigid developmental program. 

Whether the DNA replication checkpoint directly affects the Plxl activation pathway for Cdc25C has not yet been established. It is possible that the replication checkpoint arrests the cell cycle prior to initiation of the Plxl kinase cascade. Further characterization of upstream components of the cascade should reveal whether it is directly regulated by replication checkpoint activation. Such a characterization will also have importance for other M phase events, inasmuch as Plxl also regulates bipolar spindle formation, APC activation and cytokinesis (Qian et al 1998, 1999). These multiple functions of Plxl are associated with changes in localization of Plxl, and are most likely mediated by protein—protein interaction with the polo box motif in the non-catalytic C-terminal half of Plxl. 

In summary, we showed that DNA damage can elicit a variety of responses in Xenopus early embryos. While y-irradiation induces apoptosis in the embryos, DSB-containing DNA prevents initiation of DNA replication in cell-free extracts derived from eggs. 

Chong JP, Thommes P, Rowles A, Mahbubani HM, Blow JJ 1997 Characterization of the Xenopus replication licensing system. Methods Enzymol 283 549-564 Dasso M, Newport JW 1990 Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro-, studies in Xenopus. Cell 61 811-823... 

In E. coli cells, DNA replication starts at a specific site called oriC. The oriC locus contains only 245 base pairs. Similar sequences are responsible for initiating the synthesis of plasmid and bacteriophage DNA. The oriC nucleotide sequence binds several units of the tetrameric form of the dnaA protein. This protein is named for the gene that encodes it. The dnaB and dnaC proteins then bind to the complex. As a result of binding these proteins, a portion of the helical DNA is unwound. This forces the rest of the DNA into a left-handed double helix that wraps around the proteins to give a structure... 

Initial studies in mice lead to a classification of histone variants into three main subgroups on the basis of their expression and integration into chromosomes (Isenberg 1979). These are DNA replication-dependent, replication-independent. 

Moreover, overexpression of the same mutants inhibit DNA replication and block the cells at the Gl/S-phase transition (Kim et al, 2005), emphasizing the potential role of nucleolin mobilization. It is therefore highly probable that two different processes help the formation of RPA-nucleolin complexes after a genotoxic stress a post-transcriptional modification of nucleolin that renders the GAR domain of nucleolin accessible to RPA, and its p53-dependent relocalization to the nucleoplasm where a higher amount of RPA is available. Of importance, nucleolin relocalization is transient and lasts far less than replication inhibition (Daniely and Borowiec, 2000). This means that nucleolin-RPA interaction is only an initial event and that other mechanisms account for prolonged replication inhibition. 

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