scholarly journals Possible role of H1 histone in replication timing

2014 ◽  
Vol 57 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Reed A. Flickinger
Keyword(s):  
Replication Timing ◽  
H1 Histone

scholarly journals The Protective Role of Dormant Origins in Response to Replicative Stress

2018 ◽  
Vol 19 (11) ◽  
pp. 3569 ◽  
Author(s):  
Lilas Courtot ◽  
Jean-Sébastien Hoffmann ◽  
Valérie Bergoglio
Keyword(s):  
Dna Replication ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Replication Timing ◽  
Protective Role ◽  
Entire Genome ◽  
Replicative Stress ◽  
A Cell ◽  
The Many

Genome stability requires tight regulation of DNA replication to ensure that the entire genome of the cell is duplicated once and only once per cell cycle. In mammalian cells, origin activation is controlled in space and time by a cell-specific and robust program called replication timing. About 100,000 potential replication origins form on the chromatin in the gap 1 (G1) phase but only 20–30% of them are active during the DNA replication of a given cell in the synthesis (S) phase. When the progress of replication forks is slowed by exogenous or endogenous impediments, the cell must activate some of the inactive or “dormant” origins to complete replication on time. Thus, the many origins that may be activated are probably key to protect the genome against replication stress. This review aims to discuss the role of these dormant origins as safeguards of the human genome during replicative stress.

scholarly journals The Rpd3-Sin3 Histone Deacetylase Regulates Replication Timing and Enables Intra-S Origin Control in Saccharomyces cerevisiae

2004 ◽  
Vol 24 (11) ◽  
pp. 4769-4780 ◽  
Author(s):  
Jennifer G. Aparicio ◽  
Christopher J. Viggiani ◽  
Daniel G. Gibson ◽  
Oscar M. Aparicio
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Deacetylase ◽  
Transcriptional Repression ◽  
Replication Timing ◽  
Histone Deacetylation ◽  
Origin Firing ◽  
Replication Checkpoint ◽  
Genome Transcription ◽  
Late Origin

ABSTRACT The replication of eukaryotic genomes follows a temporally staged program, in which late origin firing often occurs within domains of altered chromatin structure(s) and silenced genes. Histone deacetylation functions in gene silencing in some late-replicating regions, prompting an investigation of the role of histone deacetylation in replication timing control in Saccharomyces cerevisiae. Deletion of the histone deacetylase Rpd3 or its interacting partner Sin3 caused early activation of late origins at internal chromosomal loci but did not alter the initiation timing of early origins or a late-firing, telomere-proximal origin. By delaying initiation relative to the earliest origins, Rpd3 enables regulation of late origins by the intra-S replication checkpoint. RPD3 deletion suppresses the slow S phase of clb5Δ cells by enabling late origins to fire earlier, suggesting that Rpd3 modulates the initiation timing of many origins throughout the genome. Examination of factors such as Ume6 that function together with Rpd3 in transcriptional repression indicates that Rpd3 regulates origin initiation timing independently of its role in transcriptional repression. This supports growing evidence that for much of the S. cerevisiae genome transcription and replication timing are not linked.

scholarly journals X chromosome choice occurs independently of asynchronous replication timing

2005 ◽  
Vol 168 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Joost Gribnau ◽  
Sandra Luikenhuis ◽  
Konrad Hochedlinger ◽  
Kim Monkhorst ◽  
Rudolf Jaenisch
Keyword(s):  
X Chromosome ◽  
Molecular Mechanisms ◽  
Replication Timing ◽  
S Phase ◽  
X Inactivation ◽  
Wild Type ◽  
Gene Deletions ◽  
Asynchronous Replication ◽  
Skewed X Inactivation

In mammals, dosage compensation is achieved by X chromosome inactivation in female cells. Xist is required and sufficient for X inactivation, and Xist gene deletions result in completely skewed X inactivation. In this work, we analyzed skewing of X inactivation in mice with an Xist deletion encompassing sequence 5 KB upstream of the promoter through exon 3. We found that this mutation results in primary nonrandom X inactivation in which the wild-type X chromosome is always chosen for inactivation. To understand the molecular mechanisms that affect choice, we analyzed the role of replication timing in X inactivation choice. We found that the two Xist alleles and all regions tested on the X chromosome replicate asynchronously before the start of X inactivation. However, analysis of replication timing in cell lines with skewed X inactivation showed no preference for one of the two Xist alleles to replicate early in S-phase before the onset of X inactivation, indicating that asynchronous replication timing does not play a role in skewing of X inactivation.

scholarly journals Xenopus Cdc7 executes its essential function early in S phase and is counteracted by checkpoint-regulated protein phosphatase 1

Open Biology ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 130138 ◽  
Author(s):  
Wei Theng Poh ◽  
Gaganmeet Singh Chadha ◽  
Peter J. Gillespie ◽  
Philipp Kaldis ◽  
J. Julian Blow
Keyword(s):  
Protein Phosphatase ◽  
Replication Timing ◽  
S Phase ◽  
Replication Initiation ◽  
Protein Phosphatase 1 ◽  
Checkpoint Kinases ◽  
Anti Cancer ◽  
Egg Extracts ◽  
Mcm Proteins

The initiation of DNA replication requires two protein kinases: cyclin-dependent kinase (Cdk) and Cdc7. Although S phase Cdk activity has been intensively studied, relatively little is known about how Cdc7 regulates progression through S phase. We have used a Cdc7 inhibitor, PHA-767491, to dissect the role of Cdc7 in Xenopus egg extracts. We show that hyperphosphorylation of mini-chromosome maintenance (MCM) proteins by Cdc7 is required for the initiation, but not for the elongation, of replication forks. Unlike Cdks, we demonstrate that Cdc7 executes its essential functions by phosphorylating MCM proteins at virtually all replication origins early in S phase and is not limiting for progression through the Xenopus replication timing programme. We demonstrate that protein phosphatase 1 (PP1) is recruited to chromatin and rapidly reverses Cdc7-mediated MCM hyperphosphorylation. Checkpoint kinases induced by DNA damage or replication inhibition promote the association of PP1 with chromatin and increase the rate of MCM dephosphorylation, thereby counteracting the previously completed Cdc7 functions and inhibiting replication initiation. This novel mechanism for regulating Cdc7 function provides an explanation for previous contradictory results concerning the control of Cdc7 by checkpoint kinases and has implications for the use of Cdc7 inhibitors as anti-cancer agents.

scholarly journals Influence of change in the proportion of H1 histone variants on microsporogenesis and development of male gametophyte in transgenic plants of tobacco (Nicotiana tabacum L.)

2011 ◽  
Vol 72 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Joanna Ślusarczyk ◽  
Andrzej Wierzbicki ◽  
Marcin Przewłoka ◽  
Teresa Tykarska ◽  
Andrzej Jerzmanowski ◽  
...  
Keyword(s):  
Male Gametophyte ◽  
Pollen Grains ◽  
Histone Variants ◽  
Ultrastructural Changes ◽  
Control Group ◽  
H1 Histone ◽  
Nicotiana Tabacum L ◽  
Sterile Pollen ◽  
Different Levels

As continuation of investigations in to the mechanism of the role of the H1 histone, which is a crucial protein component chromosomes of all eukaryotes, transgenic tobacco plants with different levels of the H1 histone variants were examined. Tobacco has six sequential variants of the H1 histone: two major ones (H1A and H1B), constituting ca. 90% of all H1, and four minor ones (H1C, H1D, H1E and H1F), occurring in very small quantities. The following groups of plants were examined: K - control group with a full set of histone variants; -AB -with the A and B variants removed; -ABCD - with the A, B, C and D variants removed; and -CD - with the C and D variants removed. The analysis of microsporogenesis in those plants, based on preparations squeezed in acetoorcein, revealed the asynchronous course of meiosis in -AB and -ABCD plants, occurrence of chromosomal aberration, and, consequently, the formation of sterile pollen grains (accordingly: 84,4% and 81,4%). In -CD plants, the percentage of aberration and sterile pollen grains was similar to the control material. Electron microscope observations of microsporogenesis showed ultrastructural changes. In -AB and -ABCD plants, a major portion of the pollen grains were degraded. The smallest number of degraded pollen grains, in comparison with the control, was found in the -CD group.

Possible role of H1 histone in the differentiation of mouse erythroleukemia cells

1990 ◽  
Vol 14 (5) ◽  
pp. 457-462 ◽  
Author(s):  
FLICKINGER ◽  
BROOKS ◽  
CHOI ◽  
MORLOCK ◽  
PARKER ◽  
...  
Keyword(s):  
H1 Histone ◽  
Erythroleukemia Cells ◽  
Mouse Erythroleukemia

scholarly journals The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation

2011 ◽  
Vol 22 (10) ◽  
pp. 1753-1765 ◽  
Author(s):  
Hui-Yong Lian ◽  
E. Douglas Robertson ◽  
Shin-ichiro Hiraga ◽  
Gina M. Alvino ◽  
David Collingwood ◽  
...  
Keyword(s):  
Telomere Length ◽  
Replication Timing ◽  
Repeat Length ◽  
Genome Integrity ◽  
Histone Tail ◽  
Telomere Repeat ◽  
Replication Time ◽  
Genome Wide ◽  
Telomere Replication

DNA replication in Saccharomyces cerevisiae proceeds according to a temporal program. We have investigated the role of the telomere-binding Ku complex in specifying late replication of telomere-proximal sequences. Genome-wide analysis shows that regions extending up to 80 kb from telomeres replicate abnormally early in a yku70 mutant. We find that Ku does not appear to regulate replication time by binding replication origins directly, nor is its effect on telomere replication timing mediated by histone tail acetylation. We show that Ku instead regulates replication timing through its effect on telomere length, because deletion of the telomerase regulator Pif1 largely reverses the short telomere defect of a yku70 mutant and simultaneously rescues its replication timing defect. Consistent with this conclusion, deleting the genome integrity component Elg1 partially rescued both length and replication timing of yku70 telomeres. Telomere length–mediated control of replication timing requires the TG1–3 repeat-counting component Rif1, because a rif1 mutant replicates telomeric regions early, despite having extended TG1–3 tracts. Overall, our results suggest that the effect of Ku on telomere replication timing results from its impact on TG1–3 repeat length and support a model in which Rif1 measures telomere repeat length to ensure that telomere replication timing is correctly programmed.

scholarly journals Population sequencing data reveal a compendium of mutational processes in human germline

2020 ◽  
Author(s):  
Vladimir B. Seplyarskiy ◽  
Ruslan A. Soldatov ◽  
Ryan J. McGinty ◽  
Jakob M. Goldmann ◽  
Ryan Hernandez ◽  
...  
Keyword(s):  
Large Scale ◽  
Replication Timing ◽  
Mutagenic Effect ◽  
Dna Lesions ◽  
Sequencing Data ◽  
Biological Interpretation ◽  
Mutagenic Process ◽  
Mutational Processes ◽  
Transcription And Replication

Mechanistic processes underlying human germline mutations remain largely unknown. Variation in mutation rate and spectra along the genome is informative about the biological mechanisms. We statistically decompose this variation into separate processes using a blind source separation technique. The analysis of a large-scale whole genome sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. Seven of these processes lend themselves to a biological interpretation. One process is driven by bulky DNA lesions that resolve asymmetrically with respect to transcription and replication. Two processes independently track direction of replication fork and replication timing. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions. We also demonstrate that a recently discovered mutagenic process specific to oocytes can be localized solely from population sequencing data. This process is spread across all chromosomes and is highly asymmetric with respect to the direction of transcription, suggesting a major role of DNA damage.

scholarly journals Nuclear organisation and replication timing are coupled through RIF1–PP1 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stefano Gnan ◽  
Ilya M. Flyamer ◽  
Kyle N. Klein ◽  
Eleonora Castelli ◽  
Alexander Rapp ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Nuclear Architecture ◽  
Replication Timing ◽  
Function Approach ◽  
Dual Function ◽  
Genome Organisation ◽  
Full Complement ◽  
Nuclear Organisation ◽  
Molecular Bases

AbstractThree-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub that co-regulates both processes. Both nuclear organisation and replication timing depend upon the interaction between RIF1 and PP1. However, whereas nuclear architecture requires the full complement of RIF1 and its interaction with PP1, replication timing is not sensitive to RIF1 dosage. The role of RIF1 in replication timing also extends beyond its interaction with PP1. Availing of this separation-of-function approach, we have therefore identified in RIF1 dual function the molecular bases of the co-dependency of the replication-timing programme and nuclear architecture.

The role of H1 histone phosphorylation in the cell cycle

1978 ◽  
Vol 111 (2) ◽  
pp. 343-351 ◽  
Author(s):  
Harry R. Matthews ◽  
E.Morton Bradbury
Keyword(s):  
Cell Cycle ◽  
Histone Phosphorylation ◽  
H1 Histone
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