Metazoan origins of DNA replication: Regulation through dynamic chromatin structure

2009 ◽  
Vol 106 (4) ◽  
pp. 512-520 ◽  
Author(s):  
E. Rampakakis ◽  
D.N. Arvanitis ◽  
D. Di Paola ◽  
M. Zannis-Hadjopoulos
Keyword(s):  
Dna Replication ◽  
Chromatin Structure ◽  
Replication Regulation

scholarly journals Remodeler Catalyzed Nucleosome Repositioning: Influence of Structure and Stability

2020 ◽  
Vol 22 (1) ◽  
pp. 76
Author(s):  
Aaron Morgan ◽  
Sarah LeGresley ◽  
Christopher Fischer
Keyword(s):  
Free Energy ◽  
Dna Replication ◽  
Recent Work ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Genetic Information ◽  
Molecular Machines ◽  
Mechanical Work ◽  
Eukaryotic Genome ◽  
Hydrolysis Of

The packaging of the eukaryotic genome into chromatin regulates the storage of genetic information, including the access of the cell’s DNA metabolism machinery. Indeed, since the processes of DNA replication, translation, and repair require access to the underlying DNA, several mechanisms, both active and passive, have evolved by which chromatin structure can be regulated and modified. One mechanism relies upon the function of chromatin remodeling enzymes which couple the free energy obtained from the binding and hydrolysis of ATP to the mechanical work of repositioning and rearranging nucleosomes. Here, we review recent work on the nucleosome mobilization activity of this essential family of molecular machines.

scholarly journals DNA Replication in Quiescent Cell Nuclei: Regulation by the Nuclear Envelope and Chromatin Structure

1999 ◽  
Vol 10 (12) ◽  
pp. 4091-4106 ◽  
Author(s):  
Zhi Hong Lu ◽  
Hongzhi Xu ◽  
Gregory H. Leno
Keyword(s):  
Dna Replication ◽  
Nuclear Envelope ◽  
Chromatin Structure ◽  
Cell Nuclei ◽  
Free System ◽  
Replication Complex ◽  
Linker Histones ◽  
Egg Extract ◽  
Initiation Of Replication ◽  
Stable Association

Quiescent nuclei from differentiated somatic cells can reacquire pluripotence, the capacity to replicate, and reinitiate a program of differentiation after transplantation into amphibian eggs. The replication of quiescent nuclei is recapitulated in extracts derived from activated Xenopus eggs; therefore, we have exploited this cell-free system to explore the mechanisms that regulate initiation of replication in nuclei from terminally differentiatedXenopus erythrocytes. We find that these nuclei lack many, if not all, pre-replication complex (pre-RC) proteins. Pre-RC proteins from the extract form a stable association with the chromatin of permeable nuclei, which replicate in this system, but not with the chromatin of intact nuclei, which do not replicate, even though these proteins cross an intact nuclear envelope. During extract incubation, the linker histones H1 and H10 are removed from erythrocyte chromatin by nucleoplasmin. We show that H1 removal facilitates the replication of permeable nuclei by increasing the frequency of initiation most likely by promoting the assembly of pre-RCs on chromatin. These data indicate that initiation in erythrocyte nuclei requires the acquisition of pre-RC proteins from egg extract and that pre-RC assembly requires the loss of nuclear envelope integrity and is facilitated by the removal of linker histone H1 from chromatin.

scholarly journals Control of DNA Replication: Regulation and Activation of Eukaryotic Replicative Helicase, MCM

IUBMB Life ◽  
2005 ◽  
Vol 57 (4-5) ◽  
pp. 323-335 ◽  
Author(s):  
Hisao Masai ◽  
Zhiying You ◽  
Ken-ichi Arai
Keyword(s):  
Dna Replication ◽  
Replicative Helicase ◽  
Replication Regulation

scholarly journals Activation of the DNA Damage Checkpoint in Yeast Lacking the Histone Chaperone Anti-Silencing Function 1

2004 ◽  
Vol 24 (23) ◽  
pp. 10313-10327 ◽  
Author(s):  
Christopher Josh Ramey ◽  
Susan Howar ◽  
Melissa Adkins ◽  
Jeffrey Linger ◽  
Judson Spicer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Chromatin Structure ◽  
Fluorescent Protein ◽  
Histone Chaperone ◽  
Dna Damage Checkpoint ◽  
Genomic Integrity ◽  
Dna Breaks ◽  
Double Strand Dna

ABSTRACT The packaging of the eukaryotic genome into chromatin is likely to be important for the maintenance of genomic integrity. Chromatin structures are assembled onto newly synthesized DNA by the action of chromatin assembly factors, including anti-silencing function 1 (ASF1). To investigate the role of chromatin structure in the maintenance of genomic integrity, we examined budding yeast lacking the histone chaperone Asf1p. We found that yeast lacking Asf1p accumulate in metaphase of the cell cycle due to activation of the DNA damage checkpoint. Furthermore, yeast lacking Asf1p are highly sensitive to mutations in DNA polymerase alpha and to DNA replicational stresses. Although yeast lacking Asf1p do complete DNA replication, they have greatly elevated rates of DNA damage occurring during DNA replication, as indicated by spontaneous Ddc2p-green fluorescent protein foci. The presence of elevated levels of spontaneous DNA damage in asf1 mutants is due to increased DNA damage, rather than the failure to repair double-strand DNA breaks, because asf1 mutants are fully functional for double-strand DNA repair. Our data indicate that the altered chromatin structure in asf1 mutants leads to elevated rates of spontaneous recombination, mutation, and DNA damage foci formation arising during DNA replication, which in turn activates cell cycle checkpoints that respond to DNA damage.

scholarly journals Molecular mechanics and DNA replication regulation

HFSP Journal ◽  
2007 ◽  
Vol 1 (4) ◽  
pp. 215-219 ◽  
Author(s):  
Arturo Falaschi ◽  
Gulnara Abdurashidova
Keyword(s):  
Dna Replication ◽  
Molecular Mechanics ◽  
Replication Regulation

scholarly journals Essential histone chaperones collaborate to regulate transcription and chromatin integrity

2020 ◽  
Author(s):  
Olga Viktorovskaya ◽  
James Chuang ◽  
Dhawal Jain ◽  
Natalia I. Reim ◽  
Francheska López-Rivera ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Replication ◽  
Chromatin Structure ◽  
Elongation Factor ◽  
Physical Interaction ◽  
Dependent Manner ◽  
Histone Chaperones ◽  
Transcription Elongation Factor ◽  
Nucleosome Organization ◽  
Chromatin Integrity

SUMMARYHistone chaperones are critical for controlling chromatin integrity during transcription, DNA replication, and DNA repair. We have discovered that the physical interaction between two essential histone chaperones, Spt6 and Spn1/Iws1, is required for transcriptional accuracy and nucleosome organization. To understand this requirement, we have isolated suppressors of an spt6 mutation that disrupts the Spt6-Spn1 interaction. Several suppressors are in a third essential histone chaperone, FACT, while another suppressor is in the transcription elongation factor Spt5/DSIF. The FACT suppressors weaken FACT-nucleosome interactions and bypass the requirement for Spn1, possibly by restoring a necessary balance between Spt6 and FACT on chromatin. In contrast, the Spt5 suppressor modulates Spt6 function in a Spn1-dependent manner. Despite these distinct mechanisms, both suppressors alleviate the nucleosome organization defects caused by disruption of the Spt6-Spn1 interaction. Taken together, we have uncovered a network in which histone chaperones and other elongation factors coordinate transcriptional integrity and chromatin structure.

scholarly journals Mechanics of DNA Replication and Transcription Guide the Asymmetric Distribution of RNAPol2 and Nucleosomes on Replicated Daughter Genomes

2019 ◽  
Author(s):  
Rahima Ziane ◽  
Alain Camasses ◽  
Marta Radman-Livaja
Keyword(s):  
Dna Replication ◽  
Chromatin Structure ◽  
Replication Timing ◽  
Gene Copy ◽  
Asymmetric Distribution ◽  
Chromatin States ◽  
Gene Copies ◽  
Active Transcription ◽  
Leading Strand ◽  
Yeast Genes

AbstractEukaryotic DNA replication occurs in the context of chromatin. Chromatin in its capacity as a transcription regulator, is also thought to have a role in the epigenetic transmission of transcription states from one cell generation to the next. It is still unclear how chromatin structure survives the disruptions of nucleosomal architecture during genomic replication or if chromatin features are indeed instructive of the transcription state of the underlying gene. We have therefore developed a method for measuring chromatin structure dynamics after replication – ChIP -NChAP (Chromatin Immuno-Precipitation - Nascent Chromatin Avidin Pulldown) - which we used to monitor the distribution of RNAPol2 and new and old H3 histones on newly-replicated daughter genomes in S. Cerevisiae. The strand specificity of our sequencing libraries allowed us to uncover the inherently asymmetric distribution of RNAPol2, H3K56ac (a mark of new histones), and H3K4me3 and H3K36me3 (“active transcription marks” used as proxies for old histones) on daughter chromatids. We find a difference in the timing of lagging and leading strand replication on the order of minutes at a majority of yeast genes. Nucleosomes and RNAPol2 preferentially bind to either the leading or the lagging strand gene copy depending on which one replicated first and RNAPol2 then shifts to the sister copy after its synthesis has completed. Our results suggest that active transcription states are inherited simultaneously and independently of their underlying active chromatin states through the recycling of the transcription machinery and old histones, respectively. We find that “active” histone marks do not instruct the cell to reestablish the same active transcription state at its underlying genes. We propose that rather than being a consequence of chromatin state inheritance transcription actually contributes to the reestablishment of chromatin states on both replicated gene copies. Our findings are consistent with a two-step model of chromatin assembly and RNAPol2 binding to nascent DNA that is based on local differences in replication timing between the lagging and leading strand. The model describes how chromatin and transcription states are first restored on one and then the other replicated gene copy, thus ensuring that after division each cell will have “inherited” a gene copy with identical gene expression and chromatin states.

scholarly journals Replication Initiation Patterns in the β-Globin Loci of Totipotent and Differentiated Murine Cells: Evidence for Multiple Initiation Regions

2002 ◽  
Vol 22 (2) ◽  
pp. 442-452 ◽  
Author(s):  
Mirit I. Aladjem ◽  
Luo Wei Rodewald ◽  
Chii Mai Lin ◽  
Sarah Bowman ◽  
Daniel M. Cimbora ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Replication ◽  
Embryonic Stem Cells ◽  
Chromatin Structure ◽  
Embryonic Stem ◽  
Replication Initiation ◽  
Globin Genes ◽  
Primary Sequence ◽  
Differentiated Cells ◽  
Hypersensitive Sites

ABSTRACT The replication initiation pattern of the murine β-globin locus was analyzed in totipotent embryonic stem cells and in differentiated cell lines. Initiation events in the murine β-globin locus were detected in a region extending from the embryonic Ey gene to the adult βminor gene, unlike the restricted initiation observed in the human locus. Totipotent and differentiated cells exhibited similar initiation patterns. Deletion of the region between the adult globin genes did not prevent initiation in the remainder of the locus, suggesting that the potential to initiate DNA replication was not contained exclusively within the primary sequence of the deleted region. In addition, a deletion encompassing the six identified 5′ hypersensitive sites in the mouse locus control region had no effect on initiation from within the locus. As this deletion also did not affect the chromatin structure of the locus, we propose that the sequences determining both chromatin structure and replication initiation lie outside the hypersensitive sites removed by the deletion.

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