scholarly journals Replication-Coupled Chromatin Remodeling: An Overview of Disassembly and Assembly of Chromatin during Replication

2021 ◽  
Vol 22 (3) ◽  
pp. 1113
Author(s):  
Céline Duc ◽  
Christophe Thiriet
Keyword(s):  
Cell Cycle ◽  
Chromatin Remodeling ◽  
Nuclear Import ◽  
Genomic Dna ◽  
Epigenetic Inheritance ◽  
S Phase ◽  
Chromatin Assembly ◽  
Present Review ◽  
Replication Forks ◽  
Replication Machinery

The doubling of genomic DNA during the S-phase of the cell cycle involves the global remodeling of chromatin at replication forks. The present review focuses on the eviction of nucleosomes in front of the replication forks to facilitate the passage of replication machinery and the mechanism of replication-coupled chromatin assembly behind the replication forks. The recycling of parental histones as well as the nuclear import and the assembly of newly synthesized histones are also discussed with regard to the epigenetic inheritance.

scholarly journals Mitotic replisome disassembly in vertebrates

2018 ◽  
Author(s):  
Sara Priego Moreno ◽  
Rebecca M. Jones ◽  
Divyasree Poovathumkadavil ◽  
Agnieszka Gambus
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Ubiquitin Ligase ◽  
S Phase ◽  
Replication Forks ◽  
Replication Machinery ◽  
Replicative Helicase ◽  
Egg Extract ◽  
Eukaryotic Dna ◽  
Higher Eukaryotes

ABSTRACTRecent years have brought a breakthrough in our understanding of the process of eukaryotic DNA replication termination. We have shown that the process of replication machinery (replisome) disassembly at the termination of DNA replication forks in S-phase of the cell cycle is driven through polyubiquitylation of one of the replicative helicase subunits Mcm7. Our previous work in C.elegans embryos suggested also an existence of a back-up pathway of replisome disassembly in mitosis. Here we show, that in Xenopus laevis egg extract, any replisome retained on chromatin after S-phase is indeed removed from chromatin in mitosis. This mitotic disassembly pathway depends on formation of K6 and K63 ubiquitin chains on Mcm7 by TRAIP ubiquitin ligase and activity of p97/VCP protein segregase. The mitotic replisome pathway is therefore conserved through evolution in higher eukaryotes. However, unlike in lower eukaryotes it does not require SUMO modifications. This process can also remove any helicases from chromatin, including “active” stalled ones, indicating a much wider application of this pathway than just a “back-up” for terminated helicases.

scholarly journals H4 replication-dependent diacetylation and Hat1 promote S-phase chromatin assembly in vivo

2011 ◽  
Vol 22 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Aïda Ejlassi-Lassallette ◽  
Eloïse Mocquard ◽  
Marie-Claire Arnaud ◽  
Christophe Thiriet
Keyword(s):  
Recombinant Proteins ◽  
Nuclear Import ◽  
Posttranslational Modification ◽  
Histone Acetyltransferase ◽  
S Phase ◽  
Chromatin Assembly ◽  
Replication Forks ◽  
Tail Domain ◽  
Type B

While specific posttranslational modification patterns within the H3 and H4 tail domains are associated with the S-phase, their actual functions in replication-dependent chromatin assembly have not yet been defined. Here we used incorporation of trace amounts of recombinant proteins into naturally synchronous macroplasmodia of Physarum polycephalum to examine the function of H3 and H4 tail domains in replication-coupled chromatin assembly. We found that the H3/H4 complex lacking the H4 tail domain was not efficiently recovered in nuclei, whereas depletion of the H3 tail domain did not impede nuclear import but chromatin assembly failed. Furthermore, our results revealed that the proper pattern of acetylation on the H4 tail domain is required for nuclear import and chromatin assembly. This is most likely due to binding of Hat1, as coimmunoprecipitation experiments showed Hat1 associated with predeposition histones in the cytoplasm and with replicating chromatin. These results suggest that the type B histone acetyltransferase assists in shuttling the H3/H4 complex from cytoplasm to the replication forks.

scholarly journals Chk1 Phosphorylates Cdh1 to Promote SCFβTRCP-Dependent Degradation of Cdh1 During S-Phase

2019 ◽  
Author(s):  
Debjani Pal ◽  
Adrian E. Torres ◽  
Abbey L. Messina ◽  
Andrew Dickson ◽  
Kuntal De ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Feedback Loop ◽  
Cellular Proliferation ◽  
Genomic Stability ◽  
Cyclin A ◽  
S Phase ◽  
Anaphase Promoting Complex ◽  
Replication Machinery ◽  
Key Factor ◽  
Phase Entry

ABSTRACTThe interplay of the Anaphase-Promoting Complex/Cyclosome (APC/C) and Skp1-Cul1-F-box (SCF) E3 ubiquitin ligases is necessary for controlling cell cycle transitions and checkpoint responses, which are critical for maintaining genomic stability. Yet, the mechanisms underlying the coordinated activity of these enzymes are not completely understood. Recently, Cyclin A- and Plk1- mediated phosphorylation of Cdh1 was demonstrated to trigger its ubiquitination by SCFβTRCP at the G1/S transition. However, Cyclin A-Cdk and Plk1 activities peak in G2 so it is unclear why Cdh1 is targeted at G1/S but not in G2. Here, we show that phosphorylation of Cdh1 by Chk1 contributes to its recognition by SCFβTRCP, promotes efficient S-phase entry, and is important for cellular proliferation. Conversely, Chk1 activity in G2 inhibits Cdh1 accumulation. Overall, these data suggest a model whereby the rise and fall of Chk1 activity is a key factor in the feedback loop between APC/CCdh1 and the replication machinery that enhances the G1/S and S/G2 transitions, respectively.

scholarly journals The trans cell cycle effects of PARP inhibitors underlie their selectivity toward BRCA1/2-deficient cells

2021 ◽  
Author(s):  
Antoine Simoneau ◽  
Rosalinda Xiong ◽  
Lee Zou
Keyword(s):  
Cell Cycle ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
S Phase ◽  
Replication Forks ◽  
Dna Double Strand Breaks ◽  
Origin Firing ◽  
Cell Cycles ◽  
Strand Breaks ◽  
Multiple Cell

PARP inhibitor (PARPi) is widely used to treat BRCA1/2-deficient tumors, but why PARPi is more effective than other DNA-damaging drugs is unclear. Here, we show that PARPi generates DNA double-strand breaks (DSBs) predominantly in a trans cell cycle manner. During the first S phase after PARPi exposure, PARPi induces single-stranded DNA (ssDNA) gaps behind DNA replication forks. By trapping PARP on DNA, PARPi prevents the completion of gap repair until the next S phase, leading to collisions of replication forks with ssDNA gaps and a surge of DSBs. In the second S phase, BRCA1/2-deficient cells are unable to suppress origin firing through ATR, resulting in continuous DNA synthesis and more DSBs. Furthermore, BRCA1/2-deficient cells cannot recruit RAD51 to repair collapsed forks. Thus, PARPi induces DSBs progressively through trans cell cycle ssDNA gaps, and BRCA1/2-deficient cells fail to slow down and repair DSBs over multiple cell cycles, explaining the unique efficacy of PARPi in BRCA1/2-deficient cells.

scholarly journals A Novel Cell Cycle Inhibitor Stalls Replication Forks and Activates S Phase Checkpoint

Cell Cycle ◽  
2007 ◽  
Vol 6 (13) ◽  
pp. 1621-1630 ◽  
Author(s):  
Vaidehi Krishnan ◽  
Léon Dirick ◽  
Hong Hwa Lim ◽  
Tiffany Siew Joo Lim ◽  
San Ling Si-Hoe ◽  
...  
Keyword(s):  
Cell Cycle ◽  
S Phase ◽  
Replication Forks ◽  
Cell Cycle Inhibitor ◽  
S Phase Checkpoint

scholarly journals Productive herpesvirus lytic replication in primary effusion lymphoma cells requires S-phase entry

2020 ◽  
Vol 101 (8) ◽  
pp. 873-883 ◽  
Author(s):  
Robert Hollingworth ◽  
Grant S. Stewart ◽  
Roger J. Grand
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Latent Infection ◽  
Primary Effusion Lymphoma ◽  
S Phase ◽  
Lytic Replication ◽  
Replication Forks ◽  
Viral Dna ◽  
Cellular Replication ◽  
Phase Entry

Gammaherpesviruses establish lifelong latent infection in B lymphocytes and are the causative agent of several B-cell malignancies and lymphoproliferative disorders. While a quiescent latent infection allows these pathogens to evade immune detection, initiation of an alternative lifecycle stage, known as lytic replication, is an essential step in the production and dissemination of infectious progeny. Although cessation of cellular proliferation is an eventual consequence of lytic induction, exactly how gammaherpesviruses manipulate the cell cycle prior to amplification of viral DNA remains under debate. Here we show that the onset of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation in B cells leads to S-phase accumulation and that exit from G1 is required for efficient viral DNA replication. We also show that lytic replication leads to an S-phase-specific activation of the DNA damage response (DDR) that is abrogated when lytic replication is restricted to G0/G1. Finally, we observe that expression of early lytic viral genes results in cellular replication stress with increased stalling of DNA replication forks. Overall, we demonstrate that S-phase entry is important for optimal KSHV replication, that G1 arresting compounds are effective inhibitors of viral propagation, and that lytic-induced cell-cycle arrest could occur through the obstruction of cellular replication forks and subsequent activation of the DDR.

The efficiency and timing of plasmid DNA replication in Xenopus eggs: correlations to the extent of prior chromatin assembly

1992 ◽  
Vol 103 (4) ◽  
pp. 907-918 ◽  
Author(s):  
J.A. Sanchez ◽  
D. Marek ◽  
L.J. Wangh
Keyword(s):  
Cell Cycle ◽  
Enzymatic Digestion ◽  
S Phase ◽  
Chromatin Assembly ◽  
Type I ◽  
Dependent Manner ◽  
Cell Cycles ◽  
Gene Insertion ◽  
Cycle Dependent

Injection of the circular plasmid FV1 (derived from type I bovine papilloma virus) into Xenopus eggs before the start of the first cell cycle dramatically increases the efficiency of plasmid replication once eggs are chemically activated. We call this the preloading effect and report kinetic and quantitative characterization of this phenomenon here. The timing and the amount of FV1 synthesis were measured by both BrdUTP density labelling and an optimized method of selective enzymatic digestion of replicated and unreplicated molecules using the three methyladenosine-sensitive isoschizomers, DpnI, MboI and Sau3a. DpnI in 100 mM NaCl proved particularly useful for distinguishing and quantitating unreplicated, once-replicated, and repeatedly replicated molecules accumulated over several cell cycles. Our results reveal that both the amount of DNA replicated and the timing of synthesis during the first S-phase correlate with the length of the preloading period. Longer preloading leads to larger amounts of DNA being replicated sooner. In fact, up to 30–50% of 1 ng injected plasmid can replicate in a semiconservative cell cycle-dependent manner during the first S-phase. But such high levels of synthesis during the first cell cycle appear to limit the egg's ability to rereplicate this material in subsequent cell cycles. The preloading effect does not depend on synthesis of either viral or egg proteins, but does appear to correlate with the extent of plasmid assembly into chromatin before the start of the cell cycle. We postulate that each plasmid molecule must achieve a critical degree of chromatin assembly before it can proceed along the replication pathway. These observations illuminate some of the difficulties inherent in building a vector for gene insertion into Xenopus embryos, but also suggest an experimental strategy toward this aim.

scholarly journals Transcription-Associated Recombination Is Dependent on Replication in Mammalian Cells

2007 ◽  
Vol 28 (1) ◽  
pp. 154-164 ◽  
Author(s):  
Ponnari Gottipati ◽  
Tobias N. Cassel ◽  
Linda Savolainen ◽  
Thomas Helleday
Keyword(s):  
Cell Cycle ◽  
Homologous Recombination ◽  
Mammalian Cells ◽  
Strand Break ◽  
Double Strand Break ◽  
S Phase ◽  
Replication Forks ◽  
Higher Eukaryotes ◽  
Stalled Replication Forks ◽  
Gene Conversions

ABSTRACT Transcription can enhance recombination; this is a ubiquitous phenomenon from prokaryotes to higher eukaryotes. However, the mechanism of transcription-associated recombination in mammalian cells is poorly understood. Here we have developed a construct with a recombination substrate in which levels of recombination can be studied in the presence or absence of transcription. We observed a direct enhancement in recombination when transcription levels through the substrate were increased. This increase in homologous recombination following transcription is locus specific, since homologous recombination at the unrelated hprt gene is unaffected. In addition, we have shown that transcription-associated recombination involves both short-tract and long-tract gene conversions in mammalian cells, which are different from double-strand-break-induced recombination events caused by endonucleases. Transcription fails to enhance recombination in cells that are not in the S phase of the cell cycle. Furthermore, inhibition of transcription suppresses induction of recombination at stalled replication forks, suggesting that recombination may be involved in bypassing transcription during replication.

scholarly journals S-phase-dependent action of cycloheximide in relieving chromatin-mediated general transcriptional repression

1998 ◽  
Vol 336 (3) ◽  
pp. 619-624 ◽  
Author(s):  
Maya CESARI ◽  
Laurent HÉLIOT ◽  
Catherine MEPLAN ◽  
Michel PABION ◽  
Saadi KHOCHBIN
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Replication ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Chromatin Structure ◽  
Transcriptional Activation ◽  
Regulation Of Gene Expression ◽  
S Phase ◽  
Chromatin Assembly

Chromatin plays a major role in the tight regulation of gene expression and in constraining inappropriate gene activity. Replication-coupled chromatin assembly ensures maintenance of these functions of chromatin during S phase of the cell cycle. Thus treatment of cells with an inhibitor of translation, such as cycloheximide (CX), would be expected to have a dramatic effect on chromatin structure and function, essentially in S phase of the cell cycle, due to uncoupled DNA replication and chromatin assembly. In this work, we confirm this hypothesis and show that CX can induce a dramatic S-phase-dependent alteration in chromatin structure that is associated with general RNA polymerase II-dependent transcriptional activation. Using two specific RNA polymerase II-transcribed genes, we confirm the above conclusion and show that CX-mediated transcriptional activation is enhanced during the DNA replication phase of the cell cycle. Moreover, we show co-operation between an inhibitor of histone deacetylase and CX in inducing gene expression, which is again S-phase-dependent. The modest effect of CX in inducing the activity of a transiently transfected promoter shows that the presence of the promoter in an endogenous chromatin context is necessary in order to observe transcriptional activation. We therefore suggest that the uncoupled DNA replication and histone synthesis that occur after CX treatment induces a general modification of chromatin structure, and propose that this general disorganization of chromatin structure is responsible for a widespread activation of RNA polymerase II-mediated gene transcription.

scholarly journals Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis

2021 ◽  
Author(s):  
Ashley Boice ◽  
Raj Kumari Pandita ◽  
Karla Lopez ◽  
Melissa J Pourpak ◽  
Chloe I Charendoff ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
S Phase ◽  
Phase Cell ◽  
Replication Forks ◽  
Cycle Arrest ◽  
Dividing Cells ◽  
Caspase 2 ◽  
Stalled Replication Forks

In addition to its classical role in apoptosis, accumulating evidence suggests that caspase-2 has non-apoptotic functions, including regulation of cell division. Loss of caspase-2 is known to increase proliferation rates but how caspase-2 is regulating this process is currently unclear. We show that caspase-2 is activated in dividing cells in G1- and early S-phase. In the absence of caspase-2, cells exhibit numerous S-phase defects including delayed exit from S-phase, S-phase-associated chromosomal aberrations, and increased DNA damage following S-phase arrest. In addition, caspase-2-deficient cells have a higher frequency of stalled replication forks, decreased DNA fiber length, and impeded progression of DNA replication tracts. This indicates that caspase-2 reduces replication stress and promotes replication fork protection to maintain genomic stability. These functions are independent of the pro-apoptotic function of caspase-2 because blocking caspase-2-induced cell death had no effect on cell division or DNA damage-induced cell cycle arrest. Thus, our data supports a model where caspase-2 regulates cell cycle events to protect from the accumulation of DNA damage independently of its pro-apoptotic function.

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