scholarly journals HOXD13 Binds DNA Replication Origins To Promote Origin Licensing and Is Inhibited by Geminin

2009 ◽  
Vol 29 (21) ◽  
pp. 5775-5788 ◽  
Author(s):  
Valentina Salsi ◽  
Silvia Ferrari ◽  
Roberta Ferraresi ◽  
Andrea Cossarizza ◽  
Alexis Grande ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Replication Origin ◽  
Cultured Cells ◽  
Cell Aggregation ◽  
Replication Origins ◽  
Protein Activity ◽  
Hox Proteins ◽  
Origin Licensing

ABSTRACT HOX DNA-binding proteins control patterning during development by regulating processes such as cell aggregation and proliferation. Recently, a possible involvement of HOX proteins in replication origin activity was suggested by results showing that a number of HOX proteins interact with the DNA replication licensing regulator geminin and bind a characterized human origin of replication. The functional significance of these observations, however, remained unclear. We show that HOXD13, HOXD11, and HOXA13 bind in vivo all characterized human replication origins tested. We furthermore show that HOXD13 interacts with the CDC6 loading factor, promotes pre-replication complex (pre-RC) proteins assembly at origins, and stimulates DNA synthesis in an in vivo replication assay. HOXD13 expression in cultured cells accelerates DNA synthesis initiation in correlation with the earlier pre-RC recruitment onto origins during G1 phase. Geminin, which interacts with HOXD13 as well, blocks HOXD13-mediated assembly of pre-RC proteins and inhibits HOXD13-induced DNA replication. Our results uncover a function for Hox proteins in the regulation of replication origin activity and reveal an unforeseen role for the inhibition of HOX protein activity by geminin in the context of replication origin licensing.

scholarly journals Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongzheng Li ◽  
Boxin Xue ◽  
Mengling Zhang ◽  
Liwei Zhang ◽  
Yingping Hou ◽  
...  
Keyword(s):  
Dna Replication ◽  
Structural Dynamics ◽  
Replication Origin ◽  
High Efficiency ◽  
S Phase ◽  
Chromatin Domain ◽  
Replication Origins ◽  
Replication Efficiency ◽  
Topologically Associating Domains ◽  
Epigenetic Signatures

Abstract Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

Stimulation of DNA Synthesis by Mouse DNA Helicase B in a DNA Replication System Containing Eukaryotic Replication Origins

Biochemistry ◽  
1995 ◽  
Vol 34 (24) ◽  
pp. 7913-7922 ◽  
Author(s):  
Ken Matsumoto ◽  
Masayuki Seki ◽  
Chikahide Masutani ◽  
Shusuke Tada ◽  
Takemi Enomoto ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Dna Helicase ◽  
Replication Origins ◽  
Replication System ◽  
Stimulation Of

scholarly journals In vivo protein-DNA interactions at human DNA replication origin.

1996 ◽  
Vol 93 (4) ◽  
pp. 1498-1503 ◽  
Author(s):  
D. S. Dimitrova ◽  
M. Giacca ◽  
F. Demarchi ◽  
G. Biamonti ◽  
S. Riva ◽  
...  
Keyword(s):  
Dna Replication ◽  
Replication Origin ◽  
Dna Interactions ◽  
Human Dna ◽  
Protein Dna Interactions ◽  
Dna Replication Origin

scholarly journals Concerted Loading of Mcm2–7 Double Hexamers around DNA during DNA Replication Origin Licensing

Cell ◽  
2009 ◽  
Vol 139 (4) ◽  
pp. 719-730 ◽  
Author(s):  
Dirk Remus ◽  
Fabienne Beuron ◽  
Gökhan Tolun ◽  
Jack D. Griffith ◽  
Edward P. Morris ◽  
...  
Keyword(s):  
Dna Replication ◽  
Replication Origin ◽  
Origin Licensing ◽  
Dna Replication Origin

scholarly journals Specification of Regions of DNA Replication Initiation during Embryogenesis in the 65-KilobaseDNApolα-dE2F Locus of Drosophila melanogaster

1999 ◽  
Vol 19 (1) ◽  
pp. 547-555 ◽  
Author(s):  
Takayo Sasaki ◽  
Tomoyuki Sawado ◽  
Masamitsu Yamaguchi ◽  
Tomoyuki Shinomiya
Keyword(s):  
Dna Replication ◽  
Cultured Cells ◽  
Early Stage ◽  
Replication Initiation ◽  
Replication Origins ◽  
Coding Region ◽  
Promoter Regions ◽  
Dna Replication Initiation ◽  
Differentiated Cells ◽  
Active Promoter

ABSTRACT In the early stage of Drosophila embryogenesis, DNA replication initiates at unspecified sites in the chromosome. In contrast, DNA replication initiates in specified regions in cultured cells. We investigated when and where the initiation regions are specified during embryogenesis and compared them with those observed in cultured cells by two-dimensional gel methods. In the DNA polymerase α gene (DNApolα) locus, where an initiation region,oriDα, had been identified in cultured Kc cells, repression of origin activity in the coding region was detected after formation of cellular blastoderms, and the range of the initiation region had become confined by 5 h after fertilization. During this work we identified other initiation regions between oriDα and the Drosophila E2F gene (dE2F) downstream of DNApolα. At least four initiation regions showing replication bubbles were identified in the 65-kbDNApolα-dE2F locus in 5-h embryos, but only two were observed in Kc cells. These results suggest that the specification levels of origin usage in 5-h embryos are in the intermediate state compared to those in more differentiated cells. Further, we found a spatial correlation between the active promoter regions fordE2F and the active initiation zones of replication. In 5-h embryos, two known transcripts differing in their first exons were expressed, and two regions close to the respective promoter regions for both transcripts functioned as replication origins. In Kc cells, only one transcript was expressed and functional replication origins were observed only in the region including the promoter region for this transcript.

The programme of DNA replication: beyond genome duplication

2013 ◽  
Vol 41 (6) ◽  
pp. 1720-1725 ◽  
Author(s):  
Blanca Gómez-Escoda ◽  
Pei-Yun Jenny Wu
Keyword(s):  
Dna Replication ◽  
Cell Growth ◽  
Dna Synthesis ◽  
Genetic Information ◽  
Replication Origin ◽  
Genome Duplication ◽  
Replication Initiation ◽  
Origin Activation ◽  
Key Steps ◽  
Cell Growth And Proliferation

The accurate duplication and transmission of genetic information is critical for cell growth and proliferation, and this is ensured in part by the multi-layered regulation of DNA synthesis. One of the key steps in this process is the selection and activation of the sites of replication initiation, or origins, across the genome. Interestingly, origin usage changes during development and in different pathologies, suggesting an integral interplay between the establishment of replication initiation along the chromosomes and cellular function. The present review discusses how the spatiotemporal organization of replication origin activation may play crucial roles in the control of biological events.

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