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Nature Reviews. Microbiology Oct 2017It is remarkable how robustly a bacterial species can maintain its preferred size. This capacity is intimately related to control of the cell cycle: cell size and growth... (Review)
Review
It is remarkable how robustly a bacterial species can maintain its preferred size. This capacity is intimately related to control of the cell cycle: cell size and growth rate determine the duration of the cell cycle, which must accommodate the initiation and completion of DNA replication, and the assembly of the division apparatus during steady growth. Although we still lack an integrated view of the interconnections among events in the cell cycle, cell growth and cell size, the development of high-throughput imaging and image-processing protocols has stimulated a renaissance in the field. In this Review, we summarize recent findings, present simple classic models for cell size control, introduce high-throughput data-collection techniques, and explore the mechanisms that coordinate cell size with essential growth and cell cycle processes.
Topics: Bacteria; Cell Cycle; Cell Division; DNA Replication; DNA, Bacterial
PubMed: 28804128
DOI: 10.1038/nrmicro.2017.79 -
Nature Reviews. Molecular Cell Biology Jan 2023
Topics: Transcription, Genetic; DNA Replication
PubMed: 36456632
DOI: 10.1038/s41580-022-00567-7 -
Nature Reviews. Molecular Cell Biology Nov 2022
Topics: Humans; Legal Guardians; DNA Replication
PubMed: 36171436
DOI: 10.1038/s41580-022-00546-y -
Genes Dec 2021Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. The assembly of the pre-replicative complex...
Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to activation in S phase are well characterized; however, the interplay between the assembly of these complexes and the local chromatin environment is less well understood. To investigate the dynamic changes in chromatin organization at and surrounding replication origins, we used micrococcal nuclease (MNase) to generate genome-wide chromatin occupancy profiles of nucleosomes, transcription factors, and replication proteins through consecutive cell cycles in . During each G1 phase of two consecutive cell cycles, we observed the downstream repositioning of the origin-proximal +1 nucleosome and an increase in protected DNA fragments spanning the ARS consensus sequence (ACS) indicative of pre-RC assembly. We also found that the strongest correlation between chromatin occupancy at the ACS and origin efficiency occurred in early S phase, consistent with the rate-limiting formation of the Cdc45-Mcm2-7-GINS (CMG) complex being a determinant of origin activity. Finally, we observed nucleosome disruption and disorganization emanating from replication origins and traveling with the elongating replication forks across the genome in S phase, likely reflecting the disassembly and assembly of chromatin ahead of and behind the replication fork, respectively. These results provide insights into cell-cycle-regulated chromatin dynamics and how they relate to the regulation of origin activity.
Topics: Cell Cycle; Cell Cycle Proteins; Cell Division; Chromatin; DNA Replication; G1 Phase; Nucleosomes; Replication Origin; S Phase; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 34946946
DOI: 10.3390/genes12121998 -
Cell Cycle (Georgetown, Tex.) Aug 2016
Topics: DNA Damage; DNA Repair; DNA Replication; Sirtuin 2
PubMed: 27153288
DOI: 10.1080/15384101.2016.1184517 -
Development (Cambridge, England) Jul 2018Polyploid cells, which contain multiple copies of the typically diploid genome, are widespread in plants and animals. Polyploidization can be developmentally programmed... (Review)
Review
Polyploid cells, which contain multiple copies of the typically diploid genome, are widespread in plants and animals. Polyploidization can be developmentally programmed or stress induced, and arises from either cell-cell fusion or a process known as endoreplication, in which cells replicate their DNA but either fail to complete cytokinesis or to progress through M phase entirely. Polyploidization offers cells several potential fitness benefits, including the ability to increase cell size and biomass production without disrupting cell and tissue structure, and allowing improved cell longevity through higher tolerance to genomic stress and apoptotic signals. Accordingly, recent studies have uncovered crucial roles for polyploidization in compensatory cell growth during tissue regeneration in the heart, liver, epidermis and intestine. Here, we review current knowledge of the molecular pathways that generate polyploidy and discuss how polyploidization is used in tissue repair and regeneration.
Topics: Animals; Cell Division; DNA Replication; Humans; Organ Specificity; Polyploidy; Regeneration; Stress, Physiological
PubMed: 30021843
DOI: 10.1242/dev.156034 -
Nature Structural & Molecular Biology Apr 2023Genome integrity requires replication to be completed before chromosome segregation. The DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting...
Genome integrity requires replication to be completed before chromosome segregation. The DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting CDK1, which delays mitotic onset. Under-replication of common fragile sites (CFSs), however, escapes surveillance, resulting in mitotic chromosome breaks. Here we asked whether loose DRC activation induced by modest stresses commonly used to destabilize CFSs could explain this leakage. We found that tightening DRC activation or CDK1 inhibition stabilizes CFSs in human cells. Repli-Seq and molecular combing analyses showed a burst of replication initiations implemented in mid S-phase across a subset of late-replicating sequences, including CFSs, while the bulk genome was unaffected. CFS rescue and extra-initiations required CDC6 and CDT1 availability in S-phase, implying that CDK1 inhibition permits mistimed origin licensing and firing. In addition to delaying mitotic onset, tight DRC activation therefore supports replication completion of late origin-poor domains at risk of under-replication, two complementary roles preserving genome stability.
Topics: Humans; DNA Replication; S Phase; Chromosome Fragile Sites; Cell Cycle Proteins; DNA
PubMed: 37024657
DOI: 10.1038/s41594-023-00949-1 -
Current Opinion in Cell Biology Jun 2016DNA replication is essential for faithful transmission of genetic information and is intimately tied to chromosome structure and function. Genome duplication occurs in a... (Review)
Review
DNA replication is essential for faithful transmission of genetic information and is intimately tied to chromosome structure and function. Genome duplication occurs in a defined temporal order known as the replication-timing (RT) program, which is regulated during the cell cycle and development in discrete units referred to as replication domains (RDs). RDs correspond to topologically-associating domains (TADs) and are spatio-temporally compartmentalized in the nucleus. While improvements in experimental tools have begun to reveal glimpses of causality, they have also unveiled complex context-dependent relationships that challenge long recognized correlations of RT to chromatin organization and gene regulation. In particular, RDs/TADs that switch RT during development march to the beat of a different drummer.
Topics: Animals; Cell Cycle; Cell Nucleus; DNA Replication; DNA Replication Timing; Gene Expression Regulation; Genome; Humans; Transcription, Genetic
PubMed: 27115331
DOI: 10.1016/j.ceb.2016.03.022 -
The Enzymes 2023Since the discovery of DNA as the genetic material, scientists have been investigating how the information contained in this biological polymer is transmitted from...
Since the discovery of DNA as the genetic material, scientists have been investigating how the information contained in this biological polymer is transmitted from generation to generation. X-ray crystallography, and more recently, cryo-electron microscopy techniques have been instrumental in providing essential information about the structure, functions and interactions of the DNA and the protein machinery (replisome) responsible for its replication. In this chapter, we highlight several works that describe the structure and structure-function relationships of the core components of the prokaryotic and eukaryotic replisomes. We also discuss the most recent studies on the structural organization of full replisomes.
Topics: DNA Replication; Cryoelectron Microscopy; Crystallography; DNA; Microscopy, Electron
PubMed: 37945174
DOI: 10.1016/bs.enz.2023.07.004 -
Nature Structural & Molecular Biology Apr 2022
Topics: Cell Line, Tumor; DNA Replication
PubMed: 35396541
DOI: 10.1038/s41594-022-00767-x