scholarly journals Recent advancements in the discovery of protein–protein interaction inhibitors of replication protein A

MedChemComm ◽  
2017 ◽  
Vol 8 (2) ◽  
pp. 259-267 ◽  
Author(s):  
James D. Patrone ◽  
Alex G. Waterson ◽  
Stephen W. Fesik
Keyword(s):  
Dna Damage ◽  
Recent Work ◽  
Dna Damage Response ◽  
Protein Interaction ◽  
Protein Interactions ◽  
Protein A ◽  
Replication Protein A ◽  
Protein Protein Interactions ◽  
Protein Protein Interaction ◽  
Damage Response

This review summarizes recent work directed toward the discovery of selective inhibitors of the protein–protein interactions between RPA and proteins involved in the initiation of DNA damage response pathways.

scholarly journals Targeting Protein-Protein Interactions in the DNA Damage Response Pathways for Cancer Chemotherapy

2021 ◽  
Author(s):  
Kerry Silva McPherson ◽  
Dmitry Korzhnev
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Protein Interactions ◽  
Cell Cycle Progression ◽  
Protein Protein Interactions ◽  
Cycle Progression ◽  
Damage Recognition ◽  
Damage Response ◽  
Cellular Dna ◽  
Dna Damage Recognition

Cellular DNA damage response (DDR) is an extensive signaling network that orchestrates DNA damage recognition, repair and avoidance, cell cycle progression and cell death. DDR alternation is a hallmark of...

scholarly journals A computational and structural analysis of germline and somatic variants affecting the DDR mechanism, and their impact on human diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lorena Magraner-Pardo ◽  
Roman A. Laskowski ◽  
Tirso Pons ◽  
Janet M. Thornton
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Protein Interaction ◽  
Three Dimensional ◽  
Protein Protein Interaction ◽  
Variants Of Unknown Significance ◽  
Damage Response ◽  
Dna Variants ◽  
Unknown Significance

AbstractDNA-Damage Response (DDR) proteins are crucial for maintaining the integrity of the genome by identifying and repairing errors in DNA. Variants affecting their function can have severe consequences since failure to repair damaged DNA can result in cells turning cancerous. Here, we compare germline and somatic variants in DDR genes, specifically looking at their locations in the corresponding three-dimensional (3D) structures, Pfam domains, and protein–protein interaction interfaces. We show that somatic variants in metastatic cases are more likely to be found in Pfam domains and protein interaction interfaces than are pathogenic germline variants or variants of unknown significance (VUS). We also show that there are hotspots in the structures of ATM and BRCA2 proteins where pathogenic germline, and recurrent somatic variants from primary and metastatic tumours, cluster together in 3D. Moreover, in the ATM, BRCA1 and BRCA2 genes from prostate cancer patients, the distributions of germline benign, pathogenic, VUS, and recurrent somatic variants differ across Pfam domains. Together, these results provide a better characterisation of the most recurrent affected regions in DDRs and could help in the understanding of individual susceptibility to tumour development.

scholarly journals Simian Virus Large T Antigen Interacts with the N-Terminal Domain of the 70 kD Subunit of Replication Protein A in the Same Mode as Multiple DNA Damage Response Factors

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0116093 ◽  
Author(s):  
Boting Ning ◽  
Michael D. Feldkamp ◽  
David Cortez ◽  
Walter J. Chazin ◽  
Katherine L. Friedman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Protein A ◽  
Replication Protein A ◽  
Simian Virus ◽  
T Antigen ◽  
Replication Protein ◽  
Large T Antigen ◽  
Response Factors ◽  
Damage Response

scholarly journals Structural Analysis of Replication Protein A Recruitment of the DNA Damage Response Protein SMARCAL1

Biochemistry ◽  
2014 ◽  
Vol 53 (18) ◽  
pp. 3052-3061 ◽  
Author(s):  
Michael D. Feldkamp ◽  
Aaron C. Mason ◽  
Brandt F. Eichman ◽  
Walter J. Chazin
Keyword(s):  
Dna Damage ◽  
Structural Analysis ◽  
Dna Damage Response ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Damage Response

scholarly journals Adozelesin Triggers DNA Damage Response Pathways and Arrests SV40 DNA Replication through Replication Protein A Inactivation

2000 ◽  
Vol 275 (2) ◽  
pp. 1391-1397 ◽  
Author(s):  
Jen-Sing Liu ◽  
Shu-Ru Kuo ◽  
Mary M. McHugh ◽  
Terry A. Beerman ◽  
Thomas Melendy
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Dna Damage Response ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Damage Response ◽  
Sv40 Dna
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