scholarly journals Cell cycle-dependent dynamic association of cyclin/Cdk complexes with human DNA replication proteins

2002 ◽  
Vol 21 (10) ◽  
pp. 2485-2495 ◽  
Author(s):  
I. Frouin
1998 ◽  
Vol 143 (4) ◽  
pp. 911-919 ◽  
Author(s):  
Catharine E. Johnson ◽  
Paul T. Englund

Kinetoplast DNA (kDNA), the mitochondrial DNA in kinetoplastids, is a network containing several thousand topologically interlocked minicircles. We investigated cell cycle–dependent changes in the localization of kDNA replication enzymes by combining immunofluorescence with either hydroxyurea synchronization or incorporation of fluorescein–dUTP into the endogenous gaps of newly replicated minicircles. We found that while both topoisomerase II and DNA polymerase β colocalize in two antipodal sites flanking the kDNA during replication, they behave differently at other times. Polymerase β is not detected by immunofluorescence either during cell division or G1, but is abruptly detected in the antipodal sites at the onset of kDNA replication. In contrast, topoisomerase II is localized to sites at the network edge at all cell cycle stages; usually it is found in two antipodal sites, but during cytokinesis each postscission daughter network is associated with only a single site. During the subsequent G1, topoisomerase accumulates in a second localization site, forming the characteristic antipodal pattern. These data suggest that these sites at the network periphery are permanent components of the mitochondrial architecture that function in kDNA replication.


Cell Reports ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 3323-3338.e6
Author(s):  
Aftab Amin ◽  
Rentian Wu ◽  
Man Hei Cheung ◽  
John F. Scott ◽  
Ziyi Wang ◽  
...  

1991 ◽  
Vol 11 (1) ◽  
pp. 329-337 ◽  
Author(s):  
E M McIntosh ◽  
T Atkinson ◽  
R K Storms ◽  
M Smith

Comparison of the 5'-flanking regions of several cell cycle-regulated DNA replication genes of Saccharomyces cerevisiae has revealed the presence of a common sequence, 5'-ACGCGT-3', which is upstream and proximal to mapped transcription initiation sites. This sequence, which is the cleavage site for the restriction endonuclease MluI, is present twice in the upstream region of the yeast thymidylate synthase gene TMP1. Previous studies have implicated these MluI sites as critical components in the cell cycle-dependent transcription of TMP1. In this study, we examined more closely the importance of the ACGCGT sequences for the transcription of this gene. Using site-directed mutagenesis in combination with deletion analysis and subcloning experiments, we found that (i) while both of the TMP1 MluI sites contribute to the total transcription of this gene, the distal site is predominant and (ii) the 9-bp sequence ACGCGTTAA encompassing the distal MluI site exhibits properties of a cell cycle-stage dependent upstream activation sequence element. The results of this study support the notion that the ACGCGT sequence is an integral component of a transcription system which coordinates the cell cycle-dependent expression of DNA replication genes in S. cerevisiae.


Oncogene ◽  
2020 ◽  
Vol 39 (35) ◽  
pp. 5721-5733
Author(s):  
Zhen Shu ◽  
Zhen Li ◽  
Huanhuan Huang ◽  
Yan Chen ◽  
Jun Fan ◽  
...  

2019 ◽  
Vol 116 (31) ◽  
pp. 15661-15670 ◽  
Author(s):  
Xiaofeng Zhou ◽  
Jiarui Wang ◽  
Jonathan Herrmann ◽  
W. E. Moerner ◽  
Lucy Shapiro

The cell cycle-regulated methylation state of Caulobacter DNA mediates the temporal control of transcriptional activation of several key regulatory proteins. Temporally controlled synthesis of the CcrM DNA methyltransferase and Lon-mediated proteolysis restrict CcrM to a specific time in the cell cycle, thereby allowing the maintenance of the hemimethylated state of the chromosome during the progression of DNA replication. We determined that a chromosomal DNA-based platform stimulates CcrM degradation by Lon and that the CcrM C terminus both binds to its DNA substrate and is recognized by the Lon protease. Upon asymmetric cell division, swarmer and stalked progeny cells employ distinct mechanisms to control active CcrM. In progeny swarmer cells, CcrM is completely degraded by Lon before its differentiation into a replication-competent stalked cell later in the cell cycle. In progeny stalked cells, however, accumulated CcrM that has not been degraded before the immediate initiation of DNA replication is sequestered to the cell pole. Single-molecule imaging demonstrated physical anticorrelation between sequestered CcrM and chromosomal DNA, thus preventing DNA remethylation. The distinct control of available CcrM in progeny swarmer and stalked cells serves to protect the hemimethylated state of DNA during chromosome replication, enabling robustness of cell cycle progression.


2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Kang Liu ◽  
Joshua D. Graves ◽  
Yu-Ju Lee ◽  
Fang-Tsyr Lin ◽  
Weei-Chin Lin

ABSTRACT Cdk2-dependent TopBP1-treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here, we demonstrate that phosphorylation of TopBP1 by Akt coincides with cyclin A activation during S and G2 phases and switches the TopBP1-interacting partner from treslin to E2F1, which results in the termination of replication initiation. Premature activation of Akt in G1 phase causes an early switch and inhibits DNA replication. TopBP1 is often overexpressed in cancer and can bypass control by Cdk2 to interact with treslin, leading to enhanced DNA replication. Consistent with this notion, reducing the levels of TopBP1 in cancer cells restores sensitivity to a Cdk2 inhibitor. Together, our study links Cdk2 and Akt pathways to the control of DNA replication through the regulation of TopBP1-treslin interaction. These data also suggest an important role for TopBP1 in driving abnormal DNA replication in cancer.


1995 ◽  
Vol 15 (2) ◽  
pp. 883-891 ◽  
Author(s):  
M Foiani ◽  
G Liberi ◽  
G Lucchini ◽  
P Plevani

The yeast DNA polymerase alpha-primase B subunit functions in initiation of DNA replication. This protein is present in two forms, of 86 and 91 kDa, and the p91 polypeptide results from cell cycle-regulated phosphorylation of p86. The B subunit present in G1 arises by dephosphorylation of p91 while cells are exiting from mitosis, becomes phosphorylated in early S phase, and is competent and sufficient to initiate DNA replication. The B subunit transiently synthesized as a consequence of periodic transcription of the POL12 gene is phosphorylated no earlier than G2. Phosphorylation of the B subunit does not require execution of the CDC7-dependent step and ongoing DNA synthesis. We suggest that posttranslational modifications of the B subunit might modulate the role of DNA polymerase alpha-primase in DNA replication.


2018 ◽  
Vol 109 (8) ◽  
pp. 2458-2468 ◽  
Author(s):  
Keiichiro Sakuma ◽  
Eiichi Sasaki ◽  
Kenya Kimura ◽  
Koji Komori ◽  
Yasuhiro Shimizu ◽  
...  

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