scholarly journals BET proteins regulate homologous recombination-mediated DNA repair: BRCAness and implications for cancer therapy

2018 ◽  
Vol 144 (4) ◽  
pp. 755-766 ◽  
Author(s):  
Catia Mio ◽  
Lorenzo Gerratana ◽  
Marco Bolis ◽  
Federica Caponnetto ◽  
Andrea Zanello ◽  
...  
Keyword(s):  
Dna Repair ◽  
Cancer Therapy ◽  
Homologous Recombination

scholarly journals Targeting DNA Repair and Chromatin Crosstalk in Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 381
Author(s):  
Danielle P. Johnson ◽  
Mahesh B. Chandrasekharan ◽  
Marie Dutreix ◽  
Srividya Bhaskara
Keyword(s):  
Dna Repair ◽  
Cancer Therapy ◽  
Therapeutic Intervention ◽  
Synthetic Lethality ◽  
Checkpoint Proteins ◽  
Cellular Processes ◽  
Repair Pathways ◽  
Made In

Aberrant DNA repair pathways that underlie developmental diseases and cancers are potential targets for therapeutic intervention. Targeting DNA repair signal effectors, modulators and checkpoint proteins, and utilizing the synthetic lethality phenomena has led to seminal discoveries. Efforts to efficiently translate the basic findings to the clinic are currently underway. Chromatin modulation is an integral part of DNA repair cascades and an emerging field of investigation. Here, we discuss some of the key advancements made in DNA repair-based therapeutics and what is known regarding crosstalk between chromatin and repair pathways during various cellular processes, with an emphasis on cancer.

scholarly journals Harnessing the Nucleolar DNA Damage Response in Cancer Therapy

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1156
Author(s):  
Jiachen Xuan ◽  
Kezia Gitareja ◽  
Natalie Brajanovski ◽  
Elaine Sanij
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cancer Therapy ◽  
Dna Damage Response ◽  
Rrna Genes ◽  
Rrna Synthesis ◽  
Pol I ◽  
Clinical Investigations ◽  
Damage Response ◽  
Synthesis And Processing

The nucleoli are subdomains of the nucleus that form around actively transcribed ribosomal RNA (rRNA) genes. They serve as the site of rRNA synthesis and processing, and ribosome assembly. There are 400–600 copies of rRNA genes (rDNA) in human cells and their highly repetitive and transcribed nature poses a challenge for DNA repair and replication machineries. It is only in the last 7 years that the DNA damage response and processes of DNA repair at the rDNA repeats have been recognized to be unique and distinct from the classic response to DNA damage in the nucleoplasm. In the last decade, the nucleolus has also emerged as a central hub for coordinating responses to stress via sequestering tumor suppressors, DNA repair and cell cycle factors until they are required for their functional role in the nucleoplasm. In this review, we focus on features of the rDNA repeats that make them highly vulnerable to DNA damage and the mechanisms by which rDNA damage is repaired. We highlight the molecular consequences of rDNA damage including activation of the nucleolar DNA damage response, which is emerging as a unique response that can be exploited in anti-cancer therapy. In this review, we focus on CX-5461, a novel inhibitor of Pol I transcription that induces the nucleolar DNA damage response and is showing increasing promise in clinical investigations.

scholarly journals ASPM promotes homologous recombination-mediated DNA repair by safeguarding BRCA1 stability

iScience ◽  
2021 ◽  
pp. 102534
Author(s):  
Shibin Xu ◽  
Xingxuan Wu ◽  
Peipei Wang ◽  
Sheng-Li Cao ◽  
Bin Peng ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination

scholarly journals RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

2020 ◽  
Vol 117 (4) ◽  
pp. 2084-2091
Author(s):  
Jekaterina Vohhodina ◽  
Kimberly J. Toomire ◽  
Sarah A. Petit ◽  
Goran Micevic ◽  
Geeta Kumari ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Complex Formation ◽  
Illegitimate Recombination ◽  
Adp Ribosylation ◽  
Chromosomal Disorder ◽  
Nuclear Foci ◽  
Simultaneous Loss ◽  
Chromosome Integrity ◽  
Focal Structures

BRCA1 promotes error-free, homologous recombination-mediated repair (HRR) of DNA double-stranded breaks (DSBs). When excessive and uncontrolled, BRCA1 HRR activity promotes illegitimate recombination and genome disorder. We and others have observed that the BRCA1-associated protein RAP80 recruits BRCA1 to postdamage nuclear foci, and these chromatin structures then restrict the amplitude of BRCA1-driven HRR. What remains unclear is how this process is regulated. Here we report that both BRCA1 poly-ADP ribosylation (PARsylation) and the presence of BRCA1-bound RAP80 are critical for the normal interaction of BRCA1 with some of its partners (e.g., CtIP and BACH1) that are also known components of the aforementioned focal structures. Surprisingly, the simultaneous loss of RAP80 and failure therein of BRCA1 PARsylation results in the dysregulated accumulation in these foci of BRCA1 complexes. This in turn is associated with the intracellular development of a state of hyper-recombination and gross chromosomal disorder. Thus, physiological RAP80-BRCA1 complex formation and BRCA1 PARsylation contribute to the kinetics by which BRCA1 HRR-sustaining complexes normally concentrate in nuclear foci. These events likely contribute to aneuploidy suppression.

scholarly journals DNA repair pathways as targets for cancer therapy

2008 ◽  
Vol 8 (3) ◽  
pp. 193-204 ◽  
Author(s):  
Thomas Helleday ◽  
Eva Petermann ◽  
Cecilia Lundin ◽  
Ben Hodgson ◽  
Ricky A. Sharma
Keyword(s):  
Dna Repair ◽  
Cancer Therapy ◽  
Repair Pathways

scholarly journals End-resection at DNA double-strand breaks in the three domains of life

2013 ◽  
Vol 41 (1) ◽  
pp. 314-320 ◽  
Author(s):  
John K. Blackwood ◽  
Neil J. Rzechorzek ◽  
Sian M. Bray ◽  
Joseph D. Maman ◽  
Luca Pellegrini ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Domains Of Life ◽  
Strand Invasion ◽  
End Resection

During DNA repair by HR (homologous recombination), the ends of a DNA DSB (double-strand break) must be resected to generate single-stranded tails, which are required for strand invasion and exchange with homologous chromosomes. This 5′–3′ end-resection of the DNA duplex is an essential process, conserved across all three domains of life: the bacteria, eukaryota and archaea. In the present review, we examine the numerous and redundant helicase and nuclease systems that function as the enzymatic analogues for this crucial process in the three major phylogenetic divisions.

scholarly journals Survivin contributes to DNA repair by homologous recombination in breast cancer cells

2015 ◽  
Vol 155 (1) ◽  
pp. 53-63 ◽  
Author(s):  
Eloïse Véquaud ◽  
Grégoire Desplanques ◽  
Pascal Jézéquel ◽  
Philippe Juin ◽  
Sophie Barillé-Nion
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Homologous Recombination ◽  
Cancer Cells ◽  
Breast Cancer Cells
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