scholarly journals Molecular Basis of DNA Repair Defects in FUS-Associated ALS: Implications of a New Paradigm and Its Potential as Therapeutic Target

2020 ◽  
Author(s):  
Haibo Wang ◽  
Muralidhar L. Hegde
Keyword(s):  
Dna Repair ◽  
Therapeutic Target ◽  
Molecular Basis ◽  
New Paradigm

scholarly journals 216P COMMD1 in non-small cell lung cancer: A novel DNA repair protein as a therapeutic target and diagnostic biomarker

2021 ◽  
Vol 16 (4) ◽  
pp. S813
Author(s):  
A. Suraweera ◽  
P. Duijf ◽  
M. Tang ◽  
C. Jekimovs ◽  
K. Schrobback ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Target ◽  
Small Cell ◽  
Diagnostic Biomarker ◽  
Small Cell Lung ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals Frontline Maintenance Treatment for Ovarian Cancer

2021 ◽  
Vol 23 (8) ◽  
Author(s):  
Osnat Elyashiv ◽  
Yien Ning Sophia Wong ◽  
Jonathan A. Ledermann
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Dna Repair ◽  
Maintenance Treatment ◽  
Advanced Disease ◽  
Disease Recurrence ◽  
Primary Treatment ◽  
New Paradigm ◽  
Maintenance Strategies ◽  
Advanced Epithelial Ovarian Cancer

Abstract Purpose of Review Advanced epithelial ovarian cancer remains the most lethal gynaecological cancer. Most patients with advanced disease will relapse within 3 years after primary treatment with surgery and chemotherapy. Recurrences become increasing difficult to treat due to the emergence of drug resistance and 5-year survival has changed little over the last decade. Maintenance treatment, here defined as treatment given beyond primary chemotherapy, can both consolidate the response and prolong the control of disease which is an approach to improve survival. Recent Findings Here we review maintenance strategies such as targeting angiogenesis, interference of DNA repair through inhibition of PARP, combinations of targeting agents, and immunotherapy and hormonal therapy. Summary Much has been learnt from the success and challenges of these treatments that have in the last few years which led to significant reduction in disease recurrence, changed the guidelines for treatment, and established a new paradigm for the treatment of ovarian cancer.

scholarly journals Cyclin-Dependent Kinase 2 Functions in Normal DNA Repair and Is a Therapeutic Target in BRCA1-Deficient Cancers

2006 ◽  
Vol 66 (16) ◽  
pp. 8219-8226 ◽  
Author(s):  
Andrew J. Deans ◽  
Kum Kum Khanna ◽  
Carolyn J. McNees ◽  
Ciro Mercurio ◽  
Jörg Heierhorst ◽  
...  
Keyword(s):  
Dna Repair ◽  
Therapeutic Target ◽  
Cyclin Dependent Kinase

scholarly journals Molecular Basis of Substrate Recognition of Endonuclease Q from the Euryarchaeon Pyrococcus furiosus

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Miyako Shiraishi ◽  
Shigenori Iwai
Keyword(s):  
Dna Repair ◽  
Bacillus Subtilis ◽  
Substrate Specificity ◽  
Molecular Basis ◽  
Pyrococcus Furiosus ◽  
Substrate Recognition ◽  
Base Flipping ◽  
Content Type ◽  
Cleavage Activity

ABSTRACT Endonuclease Q (EndoQ), a DNA repair endonuclease, was originally identified in the hyperthermophilic euryarchaeon Pyrococcus furiosus in 2015. EndoQ initiates DNA repair by generating a nick on DNA strands containing deaminated bases and an abasic site. Although EndoQ is thought to be important for maintaining genome integrity in certain bacteria and archaea, the underlying mechanism catalyzed by EndoQ remains unclear. Here, we provide insights into the molecular basis of substrate recognition by EndoQ from P. furiosus (PfuEndoQ) using biochemical approaches. Our results of the substrate specificity range and the kinetic properties of PfuEndoQ demonstrate that PfuEndoQ prefers the imide structure in nucleobases along with the discovery of its cleavage activity toward 5,6-dihydrouracil, 5-hydroxyuracil, 5-hydroxycytosine, and uridine in DNA. The combined results for EndoQ substrate binding and cleavage activity analyses indicated that PfuEndoQ flips the target base from the DNA duplex, and the cleavage activity is highly dependent on spontaneous base flipping of the target base. Furthermore, we find that PfuEndoQ has a relatively relaxed substrate specificity; therefore, the role of EndoQ in restriction modification systems was explored. The activity of the EndoQ homolog from Bacillus subtilis was found not to be inhibited by the uracil glycosylase inhibitor from B. subtilis bacteriophage PBS1, whose genome is completely replaced by uracil instead of thymine. Our findings suggest that EndoQ not only has additional functions in DNA repair but also could act as an antiviral enzyme in organisms with EndoQ. IMPORTANCE Endonuclease Q (EndoQ) is a lesion-specific DNA repair enzyme present in certain bacteria and archaea. To date, it remains unclear how EndoQ recognizes damaged bases. Understanding the mechanism of substrate recognition by EndoQ is important to grasp genome maintenance systems in organisms with EndoQ. Here, we find that EndoQ from the euryarchaeon Pyrococcus furiosus recognizes the imide structure in nucleobases by base flipping, and the cleavage activity is enhanced by the base pair instability of the target base, along with the discovery of its cleavage activity toward 5,6-dihydrouracil, 5-hydroxyuracil, 5-hydroxycytosine, and uridine in DNA. Furthermore, a potential role of EndoQ in Bacillus subtilis as an antiviral enzyme by digesting viral genome is demonstrated.

scholarly journals Molecular basis for DNA repair synthesis on short gaps by mycobacterial Primase-Polymerase C

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nigel C. Brissett ◽  
Katerina Zabrady ◽  
Przemysław Płociński ◽  
Julie Bianchi ◽  
Małgorzata Korycka-Machała ◽  
...  
Keyword(s):  
Dna Repair ◽  
Molecular Basis ◽  
Repair Synthesis ◽  
Dna Repair Synthesis

DNA repair dysregulation from cancer driver to therapeutic target

2012 ◽  
Vol 12 (12) ◽  
pp. 801-817 ◽  
Author(s):  
Nicola J. Curtin
Keyword(s):  
Dna Repair ◽  
Therapeutic Target ◽  
Cancer Driver

Abstract 2827: Alternative non-homologous end joining DNA repair as therapeutic target in multiple myeloma

2018 ◽  
Author(s):  
Daniele Caracciolo ◽  
Martina Montesano ◽  
Emanuela Altomare ◽  
Grazia Consolo ◽  
Nicola Amodio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Dna Repair ◽  
Therapeutic Target ◽  
End Joining ◽  
Non Homologous End Joining

scholarly journals A new paradigm for the molecular basis of rubber elasticity

2015 ◽  
Vol 56 (3) ◽  
pp. 319-337 ◽  
Author(s):  
David E. Hanson ◽  
John L. Barber
Keyword(s):  
Molecular Basis ◽  
Rubber Elasticity ◽  
New Paradigm

Molecular Basis of DNA Repair Mechanisms and Syndromes

1998 ◽  
pp. 147-155 ◽  
Author(s):  
G. Weeda ◽  
J. de Boer ◽  
I. Donker ◽  
J. de Wit ◽  
S. B. Winkler ◽  
...  
Keyword(s):  
Dna Repair ◽  
Molecular Basis ◽  
Dna Repair Mechanisms ◽  
Repair Mechanisms
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