scholarly journals Comprehensive Mapping of the C-Terminus of Flap Endonuclease-1 Reveals Distinct Interaction Sites for Five Proteins That Represent Different DNA Replication and Repair Pathways

2008 ◽  
Vol 377 (3) ◽  
pp. 679-690 ◽  
Author(s):  
Zhigang Guo ◽  
Valerie Chavez ◽  
Purnima Singh ◽  
L. David Finger ◽  
Haiying Hang ◽  
...  
Keyword(s):  
Dna Replication ◽  
Flap Endonuclease 1 ◽  
Interaction Sites ◽  
C Terminus ◽  
Dna Replication And Repair ◽  
Repair Pathways ◽  
Comprehensive Mapping

scholarly journals Serotype-Specific Reorganization of the Mre11 Complex by Adenoviral E4orf3 Proteins

2005 ◽  
Vol 79 (11) ◽  
pp. 6664-6673 ◽  
Author(s):  
Travis H. Stracker ◽  
Darwin V. Lee ◽  
Christian T. Carson ◽  
Felipe D. Araujo ◽  
David A. Ornelles ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Production ◽  
Adenovirus Type ◽  
Expression Vectors ◽  
Gene Products ◽  
Late Protein ◽  
Mre11 Complex ◽  
Dna Replication And Repair ◽  
Repair Pathways ◽  
Adenovirus Type 5

ABSTRACT The early transcriptional region 4 (E4) of adenovirus type 5 (Ad5) encodes gene products that modulate splicing, apoptosis, transcription, DNA replication, and repair pathways. Viruses lacking both E4orf3 and E4orf6 have a severe replication defect, partially characterized by the formation of genome concatemers. Concatemer formation is dependent upon the cellular Mre11 complex and is prevented by both the E4orf3 and E4orf6 proteins. The Mre11/Rad50/Nbs1 proteins are targeted for proteasome-mediated degradation by the Ad5 viral E1b55K/E4orf6 complex. The expression of Ad5 E4orf3 causes a redistribution of Mre11 complex members and results in their exclusion from viral replication centers. For this study, we further analyzed the interactions of E4 proteins from different adenovirus serotypes with the Mre11 complex. Analyses of infections with serotypes Ad4 and Ad12 demonstrated that the degradation of Mre11/Rad50/Nbs1 proteins is a conserved feature of the E1b55K/E4orf6 complex. Surprisingly, Nbs1 and Rad50 were localized to the replication centers of both Ad4 and Ad12 viruses prior to Mre11 complex degradation. The transfection of expression vectors for the E4orf3 proteins of Ad4 and Ad12 did not alter the localization of Mre11 complex members. The E4orf3 proteins of Ad4 and Ad12 also failed to complement defects in both concatemer formation and late protein production of a virus with a deletion of E4. These results reveal surprising differences among the highly conserved E4orf3 proteins from different serotypes in the ability to disrupt the Mre11 complex.

scholarly journals Haloferax volcanii —a model archaeon for studying DNA replication and repair

Open Biology ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 200293
Author(s):  
Patricia Pérez-Arnaiz ◽  
Ambika Dattani ◽  
Victoria Smith ◽  
Thorsten Allers
Keyword(s):  
Dna Replication ◽  
Genetic Manipulation ◽  
Haloferax Volcanii ◽  
Cellular Biology ◽  
Phenotypic Screening ◽  
The Third ◽  
Dna Replication And Repair ◽  
Repair Pathways ◽  
Halophilic Species ◽  
The Relationship

The tree of life shows the relationship between all organisms based on their common ancestry. Until 1977, it comprised two major branches: prokaryotes and eukaryotes. Work by Carl Woese and other microbiologists led to the recategorization of prokaryotes and the proposal of three primary domains: Eukarya, Bacteria and Archaea. Microbiological, genetic and biochemical techniques were then needed to study the third domain of life. Haloferax volcanii , a halophilic species belonging to the phylum Euryarchaeota, has provided many useful tools to study Archaea, including easy culturing methods, genetic manipulation and phenotypic screening. This review will focus on DNA replication and DNA repair pathways in H. volcanii , how this work has advanced our knowledge of archaeal cellular biology, and how it may deepen our understanding of bacterial and eukaryotic processes.

scholarly journals The highly conserved nuclear lamin Ig-fold binds to PCNA: its role in DNA replication

2008 ◽  
Vol 181 (2) ◽  
pp. 269-280 ◽  
Author(s):  
Dale K. Shumaker ◽  
Liliana Solimando ◽  
Kaushik Sengupta ◽  
Takeshi Shimi ◽  
Stephen A. Adam ◽  
...  
Keyword(s):  
Dna Replication ◽  
Inhibitory Effect ◽  
Chain Elongation ◽  
Nuclear Antigen ◽  
Binding Studies ◽  
Docking Simulations ◽  
Nuclear Assembly ◽  
Nuclear Lamins ◽  
Interaction Sites ◽  
C Terminus

This study provides insights into the role of nuclear lamins in DNA replication. Our data demonstrate that the Ig-fold motif located in the lamin C terminus binds directly to proliferating cell nuclear antigen (PCNA), the processivity factor necessary for the chain elongation phase of DNA replication. We find that the introduction of a mutation in the Ig-fold, which alters its structure and causes human muscular dystrophy, inhibits PCNA binding. Studies of nuclear assembly and DNA replication show that lamins, PCNA, and chromatin are closely associated in situ. Exposure of replicating nuclei to an excess of the lamin domain containing the Ig-fold inhibits DNA replication in a concentration-dependent fashion. This inhibitory effect is significantly diminished in nuclei exposed to the same domain bearing the Ig-fold mutation. Using the crystal structures of the lamin Ig-fold and PCNA, molecular docking simulations suggest probable interaction sites. These findings also provide insights into the mechanisms underlying the numerous disease-causing mutations located within the lamin Ig-fold.

scholarly journals The stabilized Pol31–Pol3 interface counteracts Pol32 ablation with differential effects on repair

2021 ◽  
Vol 4 (9) ◽  
pp. e202101138
Author(s):  
Kenji Shimada ◽  
Monika Tsai-Pflugfelder ◽  
Niloofar Davoodi Vijeh Motlagh ◽  
Neda Delgoshaie ◽  
Jeannette Fuchs ◽  
...  
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Methyl Methanesulfonate ◽  
Replication Forks ◽  
Differential Effects ◽  
Protein Levels ◽  
Dna Replication And Repair ◽  
Interaction Domains ◽  
Repair Pathways ◽  
Break Induced Replication

DNA polymerase δ, which contains the catalytic subunit, Pol3, Pol31, and Pol32, contributes both to DNA replication and repair. The deletion of pol31 is lethal, and compromising the Pol3–Pol31 interaction domains confers hypersensitivity to cold, hydroxyurea (HU), and methyl methanesulfonate, phenocopying pol32Δ. We have identified alanine-substitutions in pol31 that suppress these deficiencies in pol32Δ cells. We characterize two mutants, pol31-T415A and pol31-W417A, which map to a solvent-exposed loop that mediates Pol31–Pol3 and Pol31–Rev3 interactions. The pol31-T415A substitution compromises binding to the Pol3 CysB domain, whereas Pol31-W417A improves it. Importantly, loss of Pol32, such as pol31-T415A, leads to reduced Pol3 and Pol31 protein levels, which are restored by pol31-W417A. The mutations have differential effects on recovery from acute HU, break-induced replication and trans-lesion synthesis repair pathways. Unlike trans-lesion synthesis and growth on HU, the loss of break-induced replication in pol32Δ cells is not restored by pol31-W417A, highlighting pathway-specific roles for Pol32 in fork-related repair. Intriguingly, CHIP analyses of replication forks on HU showed that pol32Δ and pol31-T415A indirectly destabilize DNA pol α and pol ε at stalled forks.

Differential regulation of cancer progression by CDK4/6 plays a central role in DNA replication and repair pathways

2020 ◽  
pp. canres.2121.2020
Author(s):  
Meiou Dai ◽  
Julien Boudreault ◽  
Ni Wang ◽  
Sophie Poulet ◽  
Girija Daliah ◽  
...  
Keyword(s):  
Dna Replication ◽  
Cancer Progression ◽  
Differential Regulation ◽  
Dna Replication And Repair ◽  
Repair Pathways

scholarly journals E. coli primase and DNA polymerase III holoenzyme are able to bind concurrently to a primed template during DNA replication

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Andrea Bogutzki ◽  
Natalie Naue ◽  
Lidia Litz ◽  
Andreas Pich ◽  
Ute Curth
Keyword(s):  
Dna Replication ◽  
Dna Polymerase ◽  
Protein Interactions ◽  
Dna Polymerase Iii ◽  
Protein Protein Interactions ◽  
Single Stranded Dna ◽  
E Coli ◽  
Polymerase Iii ◽  
C Terminus ◽  
Pol Iii

Abstract During DNA replication in E. coli, a switch between DnaG primase and DNA polymerase III holoenzyme (pol III) activities has to occur every time when the synthesis of a new Okazaki fragment starts. As both primase and the χ subunit of pol III interact with the highly conserved C-terminus of single-stranded DNA-binding protein (SSB), it had been proposed that the binding of both proteins to SSB is mutually exclusive. Using a replication system containing the origin of replication of the single-stranded DNA phage G4 (G4ori) saturated with SSB, we tested whether DnaG and pol III can bind concurrently to the primed template. We found that the addition of pol III does not lead to a displacement of primase, but to the formation of higher complexes. Even pol III-mediated primer elongation by one or several DNA nucleotides does not result in the dissociation of DnaG. About 10 nucleotides have to be added in order to displace one of the two primase molecules bound to SSB-saturated G4ori. The concurrent binding of primase and pol III is highly plausible, since even the SSB tetramer situated directly next to the 3′-terminus of the primer provides four C-termini for protein-protein interactions.

scholarly journals The Amazing Acrobat: Yeast’s Histone H3K56 Juggles Several Important Roles While Maintaining Perfect Balance

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 342
Author(s):  
Lihi Gershon ◽  
Martin Kupiec
Keyword(s):  
Dna Replication ◽  
Genome Stability ◽  
Entry And Exit ◽  
Yeast Saccharomyces Cerevisiae ◽  
Cellular Processes ◽  
M Phase ◽  
Dna Replication And Repair ◽  
H3k56 Acetylation ◽  
Timely Fashion ◽  
The Many

Acetylation on lysine 56 of histone H3 of the yeast Saccharomyces cerevisiae has been implicated in many cellular processes that affect genome stability. Despite being the object of much research, the complete scope of the roles played by K56 acetylation is not fully understood even today. The acetylation is put in place at the S-phase of the cell cycle, in order to flag newly synthesized histones that are incorporated during DNA replication. The signal is removed by two redundant deacetylases, Hst3 and Hst4, at the entry to G2/M phase. Its crucial location, at the entry and exit points of the DNA into and out of the nucleosome, makes this a central modification, and dictates that if acetylation and deacetylation are not well concerted and executed in a timely fashion, severe genomic instability arises. In this review, we explore the wealth of information available on the many roles played by H3K56 acetylation and the deacetylases Hst3 and Hst4 in DNA replication and repair.

scholarly journals Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1289 ◽  
Author(s):  
Xing Bian ◽  
Wenchu Lin
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Repair ◽  
Predictive Biomarkers ◽  
Replication Stress ◽  
Genotoxic Stress ◽  
Repair System ◽  
Damage Repair ◽  
Repair Pathways

Small cell lung cancer (SCLC), accounting for about 15% of all cases of lung cancer worldwide, is the most lethal form of lung cancer. Despite an initially high response rate of SCLC to standard treatment, almost all patients are invariably relapsed within one year. Effective therapeutic strategies are urgently needed to improve clinical outcomes. Replication stress is a hallmark of SCLC due to several intrinsic factors. As a consequence, constitutive activation of the replication stress response (RSR) pathway and DNA damage repair system is involved in counteracting this genotoxic stress. Therefore, therapeutic targeting of such RSR and DNA damage repair pathways will be likely to kill SCLC cells preferentially and may be exploited in improving chemotherapeutic efficiency through interfering with DNA replication to exert their functions. Here, we summarize potentially valuable targets involved in the RSR and DNA damage repair pathways, rationales for targeting them in SCLC treatment and ongoing clinical trials, as well as possible predictive biomarkers for patient selection in the management of SCLC.

Sign in / Sign up

Export Citation Format

Share Document