Faculty Opinions recommendation of Claspin, a Chk1-regulatory protein, monitors DNA replication on chromatin independently of RPA, ATR, and Rad17.

2003 ◽  
Author(s):  
Antony Carr
Keyword(s):  
Dna Replication ◽  
Regulatory Protein

Geminin Regulates Hematopoietic Stem Cell Proliferation and Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1478-1478
Author(s):  
Kathryn M. Shinnick ◽  
Kelly A. Barry ◽  
Elizabeth A. Eklund ◽  
Thomas J. McGarry
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Transcription Factors ◽  
Cell Division ◽  
Dna Replication ◽  
Hematopoietic Stem Cells ◽  
Conflicts Of Interest ◽  
Regulatory Protein ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation

Abstract Abstract 1478 Poster Board I-501 Hematopoietic stem cells supply the circulation with mature blood cells throughout life. Progenitor cell division and differentiation must be carefully balanced in order to supply the proper numbers and proportions of mature cells. The mechanisms that control the choice between continued cell division and terminal differentiation are incompletely understood. The unstable regulatory protein Geminin is thought to maintain cells in an undifferentiated state while they proliferate. Geminin is a bi-functional protein. It limits the extent of DNA replication to one round per cell cycle by binding and inhibiting the essential replication factor Cdt1. Loss of Geminin leads to replication abnormalities that activate the DNA replication checkpoint and the Fanconi Anemia (FA) pathway. Geminin also influences patterns of cell differentiation by interacting with Homeobox (Hox) transcription factors and chromatin remodeling proteins. To examine how Geminin affects the proliferation and differentiation of hematopoietic stem cells, we created a mouse strain in which Geminin is deleted from the proliferating cells of the bone marrow. Geminin deletion has profound effects on all three hematopoietic lineages. The production of mature erythrocytes and leukocytes is drastically reduced and the animals become anemic and neutropenic. In contrast, the population of megakaryocytes is dramatically expanded and the animals develop thrombocytosis. Interestingly, the number of c-Kit+ Sca1+ Lin- (KSL) stem cells is maintained, at least in the short term. Myeloid colony forming cells are also preserved, but the colonies that grow are smaller. We conclude that Geminin deletion causes a maturation arrest in some lineages and directs cells down some differentiation pathways at the expense of others. We are now testing how Geminin loss affects cell cycle checkpoint pathways, whether Geminin regulates hematopoietic transcription factors, and whether Geminin deficient cells give rise to leukemias or lymphomas. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Hepatitis B Virus DNA Replication Is Coordinated by Core Protein Serine Phosphorylation and HBx Expression

2005 ◽  
Vol 79 (15) ◽  
pp. 9810-9820 ◽  
Author(s):  
Margherita Melegari ◽  
Sarah K. Wolf ◽  
Robert J. Schneider
Keyword(s):  
Hepatitis B Virus ◽  
Dna Replication ◽  
Hepatitis B ◽  
Viral Replication ◽  
Core Protein ◽  
Regulatory Protein ◽  
Protein A ◽  
Serine Phosphorylation ◽  
Hbv Replication ◽  
B Virus

ABSTRACT The hepatitis B virus (HBV) core protein forms the capsid of viral particles and is essential for viral genome DNA replication and maturation. The C terminus of core protein contains three serines at positions 155, 162, and 170, phosphorylation of which is important for viral DNA replication. We demonstrate that the phosphorylation of these serines is stimulated by the viral HBx protein, a regulatory protein that activates signal transduction pathways and viral replication. HBx is therefore shown to stimulate HBV replication by increasing core serine phosphorylation. Mutational, biochemical, and mixing studies of C-terminal core serine mutants demonstrate that multiple serine phosphorylations occur on the same core protein. Mutation of individual core protein serines is shown to inhibit HBV replication at distinct stages corresponding to encapsidation of viral pregenomic RNA, reverse transcription, and restriction to synthesis of specific DNA replicative intermediates. We therefore demonstrate that a primary target of HBV replication that is regulated by HBx protein corresponds to increased phosphorylation of the viral core protein. We also demonstrate that core phosphorylation mediated by HBx promotes sequential progression of viral replication through the assembly of capsids primed for different stages of DNA synthesis.

scholarly journals Bromodomain Protein 4 Mediates the Papillomavirus E2 Transcriptional Activation Function

2006 ◽  
Vol 80 (9) ◽  
pp. 4276-4285 ◽  
Author(s):  
Michal-Ruth Schweiger ◽  
Jianxin You ◽  
Peter M. Howley
Keyword(s):  
Dna Replication ◽  
Transcriptional Activation ◽  
Viral Genome ◽  
Regulatory Protein ◽  
Activation Function ◽  
Transactivation Domain ◽  
Genome Maintenance ◽  
Mitotic Chromosomes ◽  
Viral Dna ◽  
Viral Dna Replication

ABSTRACT The papillomavirus E2 regulatory protein has essential roles in viral transcription and the initiation of viral DNA replication as well as for viral genome maintenance. Brd4 has recently been identified as a major E2-interacting protein and, in the case of the bovine papillomavirus type 1, serves to tether E2 and the viral genomes to mitotic chromosomes in dividing cells, thus ensuring viral genome maintenance. We have explored the possibility that Brd4 is involved in other E2 functions. By analyzing the binding of Brd4 to a series of alanine-scanning substitution mutants of the human papillomavirus type 16 E2 N-terminal transactivation domain, we found that amino acids required for Brd4 binding were also required for transcriptional activation but not for viral DNA replication. Functional studies of cells expressing either the C-terminal domain of Brd4 that can bind E2 and compete its binding to Brd4 or short interfering RNA to knock down Brd4 protein levels revealed a role for Brd4 in the transcriptional activation function of E2 but not for its viral DNA replication function. Therefore, these studies establish a broader role for Brd4 in the papillomavirus life cycle than as the chromosome tether for E2 during mitosis.

scholarly journals Claspin, a Chk1-Regulatory Protein, Monitors DNA Replication on Chromatin Independently of RPA, ATR, and Rad17

2003 ◽  
Vol 11 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Joon Lee ◽  
Akiko Kumagai ◽  
William G. Dunphy
Keyword(s):  
Dna Replication ◽  
Regulatory Protein

scholarly journals Human Cytomegalovirus UL84 Insertion Mutant Defective for Viral DNA Synthesis and Growth

2004 ◽  
Vol 78 (19) ◽  
pp. 10360-10369 ◽  
Author(s):  
Yiyang Xu ◽  
Sylvia A. Cei ◽  
Alicia Rodriguez Huete ◽  
Gregory S. Pari
Keyword(s):  
Dna Replication ◽  
Dna Synthesis ◽  
Real Time ◽  
Human Cytomegalovirus ◽  
Viral Genome ◽  
Infectious Virus ◽  
Regulatory Protein ◽  
Insertion Mutant ◽  
Viral Dna ◽  
Transfected Cells

ABSTRACT Human cytomegalovirus (HCMV) UL84 is required for oriLyt-dependent DNA replication, and evidence from transient transfection assays suggests that UL84 directly participates in DNA synthesis. In addition, because of its apparent interaction with IE2, UL84 is implicated as a possible regulatory protein. To address the role of UL84 in the context of the viral genome, we generated a recombinant HCMV bacterial artificial chromosome (BAC) construct that did not express the UL84 gene product. This construct, BAC-IN84/Ep, displayed a null phenotype in that it failed to produce infectious virus after transfection into human fibroblast cells, whereas a revertant virus readily produced viral plaques and, subsequently, infectious virus. Real-time quantitative PCR showed that BAC-IN84/Ep was defective for DNA synthesis in that no increase in the accumulation of viral DNA was observed in transfected cells. We were unable to complement BAC-IN84/Ep in trans; however, oriLyt-dependent DNA replication was observed by the cotransfection of UL84 and BAC-IN84/Ep. An analysis of viral mRNA by real-time PCR indicated that, even in the absence of DNA synthesis, all representative kinetic classes of genes were expressed in cells transfected with BAC-IN84/Ep. The detection of UL44 and IE2 by immunofluorescence in BAC-IN84/Ep-transfected cells showed that these proteins failed to partition into replication compartments, indicating that UL84 expression is essential for the formation of these proteins into replication centers within the context of the viral genome. These results show that UL84 provides an essential DNA replication function and influences the subcellular localization of other viral proteins.

Replication of Bacteriophage 186 DNA

1972 ◽  
Vol 30 ◽  
pp. 194-195
Author(s):  
Dhruba K. Chattoraj ◽  
Ross B. Inman
Keyword(s):  
Electron Microscopy ◽  
Dna Replication ◽  
Frame Of Reference ◽  
Dna Molecules ◽  
E Coli ◽  
Phage Dna ◽  
Partial Denaturation

Electron microscopy of replicating intermediates has been quite useful in understanding the mechanism of DNA replication in DNA molecules of bacteriophage, mitochondria and plasmids. The use of partial denaturation mapping has made the tool more powerful by providing a frame of reference by which the position of the replicating forks in bacteriophage DNA can be determined on the circular replicating molecules. This provided an easy means to find the origin and direction of replication in λ and P2 phage DNA molecules. DNA of temperate E. coli phage 186 was found to have an unique denaturation map and encouraged us to look into its mode of replication.

The infection and viral DNA replication ofBocavirusminute virus of canine in permissive cells and non-permissive cells

2010 ◽  
Vol 34 (8) ◽  
pp. S60-S60
Author(s):  
Yuning Sun ◽  
Fang Li ◽  
Jianming Qiu ◽  
Xiaohong Lu
Keyword(s):  
Dna Replication ◽  
Viral Dna ◽  
Viral Dna Replication
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