scholarly journals DNA damage-induced replication arrest in Xenopus egg extracts

2003 ◽  
Vol 163 (2) ◽  
pp. 245-255 ◽  
Author(s):  
Matthew P. Stokes ◽  
W. Matthew Michael
Keyword(s):  
Dna Damage ◽  
Proliferating Cell Nuclear Antigen ◽  
Replication Fork ◽  
Nuclear Antigen ◽  
Chromosomal Replication ◽  
Replication Arrest ◽  
Egg Extracts ◽  
Xenopus Egg ◽  
Xenopus Egg Extracts ◽  
Proliferating Cell

Chromosomal replication is sensitive to the presence of DNA-damaging alkylating agents, such as methyl methanesulfonate (MMS). MMS is known to inhibit replication though activation of the DNA damage checkpoint and through checkpoint-independent slowing of replication fork progression. Using Xenopus egg extracts, we now report an additional pathway that is stimulated by MMS-induced damage. We show that, upon incubation in egg extracts, MMS-treated DNA activates a diffusible inhibitor that blocks, in trans, chromosomal replication. The downstream effect of the inhibitor is a failure to recruit proliferating cell nuclear antigen, but not DNA polymerase α, to the nascent replication fork. Thus, alkylation damage activates an inhibitor that intercepts the replication pathway at a point between the polymerase α and proliferating cell nuclear antigen execution steps. We also show that activation of the inhibitor does not require the DNA damage checkpoint; rather, stimulation of the pathway described here results in checkpoint activation. These data describe a novel replication arrest pathway, and they also provide an example of how subpathways within the DNA damage response network are integrated to promote efficient cell cycle arrest in response to damaged DNA.

scholarly journals Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts

2005 ◽  
Vol 171 (6) ◽  
pp. 947-954 ◽  
Author(s):  
Craig A. Leach ◽  
W. Matthew Michael
Keyword(s):  
Xenopus Laevis ◽  
Replication Fork ◽  
Nuclear Antigen ◽  
Molecular Gas ◽  
Chromosomal Replication ◽  
Dna Templates ◽  
Replication Fork Progression ◽  
Egg Extracts ◽  
The Impact ◽  
Proliferating Cell

The homotrimeric DNA replication protein proliferating cell nuclear antigen (PCNA) is regulated by both ubiquitylation and sumoylation. We study the appearance and the impact of these modifications on chromosomal replication in frog egg extracts. Xenopus laevis PCNA is modified on lysine 164 by sumoylation, monoubiquitylation, and diubiquitylation. Sumoylation and monoubiquitylation occur during the replication of undamaged DNA, whereas diubiquitylation occurs specifically in response to DNA damage. When lysine 164 modification is prevented, replication fork movement through undamaged DNA slows down and DNA polymerase δ fails to associate with replicating chromatin. When sumoylation alone is prevented, replication occurs normally and neither monoubiquitylation nor sumoylation are required for the replication of simple single-strand DNA templates. Our findings expand the repertoire of functions for PCNA ubiquitylation and sumoylation by elucidating a role for these modifications during the replication of undamaged DNA. Furthermore, they suggest that PCNA monoubiquitylation serves as a molecular gas pedal that controls the speed of replisome movement during S phase.

scholarly journals Oxidative DNA Damage Bypass in Arabidopsis thaliana Requires DNA Polymerase λ and Proliferating Cell Nuclear Antigen 2

2011 ◽  
Vol 23 (2) ◽  
pp. 806-822 ◽  
Author(s):  
Alessandra Amoroso ◽  
Lorenzo Concia ◽  
Caterina Maggio ◽  
Cécile Raynaud ◽  
Catherine Bergounioux ◽  
...  
Keyword(s):  
Dna Damage ◽  
Arabidopsis Thaliana ◽  
Dna Polymerase ◽  
Proliferating Cell Nuclear Antigen ◽  
Oxidative Dna Damage ◽  
Nuclear Antigen ◽  
Dna Polymerase Λ ◽  
Proliferating Cell

Proliferating cell nuclear antigen destabilizes c-Abl tyrosine kinase and regulates cell apoptosis in response to DNA damage

APOPTOSIS ◽  
2009 ◽  
Vol 14 (3) ◽  
pp. 268-275 ◽  
Author(s):  
Xiang He ◽  
Congwen Wei ◽  
Ting Song ◽  
Jing Yuan ◽  
Yanhong Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tyrosine Kinase ◽  
Cell Apoptosis ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Abl Tyrosine Kinase ◽  
Proliferating Cell

Interaction between proliferating cell nuclear antigen (PCNA) and a DnaJ induced by DNA damage

2005 ◽  
Vol 118 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Taichi Yamamoto ◽  
Yoko Mori ◽  
Toyotaka Ishibashi ◽  
Yukinobu Uchiyama ◽  
Tadamasa Ueda ◽  
...  
Keyword(s):  
Dna Damage ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Proliferating Cell

scholarly journals Replication Fork Uncoupling Causes Nascent Strand Degradation and Fork Reversal

2021 ◽  
Author(s):  
Tamar Kavlashvili ◽  
James M Dewar
Keyword(s):  
Dna Replication ◽  
Replication Fork ◽  
Genome Stability ◽  
Replicative Helicase ◽  
Before And After ◽  
Egg Extracts ◽  
Xenopus Egg ◽  
Biochemical Approach ◽  
Key Steps ◽  
Xenopus Egg Extracts

Genotoxins cause nascent strand degradation (NSD) and fork reversal during DNA replication. NSD and fork reversal are crucial for genome stability and exploited by chemotherapeutic approaches. However, it is unclear how NSD and fork reversal are triggered. Additionally, the fate of the replicative helicase during these processes is unknown. We developed a biochemical approach to study synchronous, localized NSD and fork reversal using Xenopus egg extracts. We show that replication fork uncoupling stimulates NSD of both nascent strands and progressive conversion of uncoupled forks to reversed forks. The replicative helicase remains bound during NSD and fork reversal, indicating that both processes take place behind the helicase. Unexpectedly, NSD occurs before and after fork reversal, indicating that multiple degradation steps take place. Overall, our data show that uncoupling causes NSD and fork reversal and identify key steps involved in these processes.

scholarly journals Revelation of p53-independent Function of MTA1 in DNA Damage Response via Modulation of the p21WAF1-Proliferating Cell Nuclear Antigen Pathway

2010 ◽  
Vol 285 (13) ◽  
pp. 10044-10052 ◽  
Author(s):  
Da-Qiang Li ◽  
Suresh B. Pakala ◽  
Sirigiri Divijendra Natha Reddy ◽  
Kazufumi Ohshiro ◽  
Shao-Hua Peng ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Proliferating Cell Nuclear Antigen ◽  
Nuclear Antigen ◽  
Independent Function ◽  
Damage Response ◽  
Proliferating Cell

scholarly journals Replication-Fork Stalling and Processing at a Single Psoralen Interstrand Crosslink in Xenopus Egg Extracts

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18554 ◽  
Author(s):  
Cyrille Le Breton ◽  
Magali Hennion ◽  
Paola B. Arimondo ◽  
Olivier Hyrien
Keyword(s):  
Replication Fork ◽  
Interstrand Crosslink ◽  
Egg Extracts ◽  
Xenopus Egg ◽  
Replication Fork Stalling ◽  
Fork Stalling ◽  
Xenopus Egg Extracts

scholarly journals Control of PCNA deubiquitylation in yeast

2010 ◽  
Vol 38 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Alfonso Gallego-Sánchez ◽  
Francisco Conde ◽  
Pedro San Segundo ◽  
Avelino Bueno
Keyword(s):  
Dna Damage ◽  
Crucial Role ◽  
Proliferating Cell Nuclear Antigen ◽  
Molecular Mechanisms ◽  
Damage Tolerance ◽  
Nuclear Antigen ◽  
Dna Damage Tolerance ◽  
Sliding Clamp ◽  
Evolutionarily Conserved ◽  
Proliferating Cell

Eukaryotes ubiquitylate the replication factor PCNA (proliferating-cell nuclear antigen) so that it tolerates DNA damage. Although, in the last few years, the understanding of the evolutionarily conserved mechanism of ubiquitylation of PCNA, and its crucial role in DNA damage tolerance, has progressed impressively, little is known about the deubiquitylation of this sliding clamp in most organisms. In the present review, we will discuss potential molecular mechanisms regulating PCNA deubiquitylation in yeast.

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