Modulating DNA Repair Pathways to Improve Precision Genome Engineering

2017 ◽  
Vol 13 (2) ◽  
pp. 389-396 ◽  
Author(s):  
Katherine S. Pawelczak ◽  
Navnath S. Gavande ◽  
Pamela S. VanderVere-Carozza ◽  
John J. Turchi
Keyword(s):  
Dna Repair ◽  
Genome Engineering ◽  
Repair Pathways

Plant DNA Repair Pathways and Their Applications in Genome Engineering

2019 ◽  
pp. 3-24 ◽  
Author(s):  
Qiudeng Que ◽  
Zhongying Chen ◽  
Tim Kelliher ◽  
David Skibbe ◽  
Shujie Dong ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genome Engineering ◽  
Plant Dna ◽  
Repair Pathways

scholarly journals CRISPR-Cas12a induced DNA double-strand breaks are repaired by locus-dependent and error-prone pathways in a fungal pathogen

2021 ◽  
Author(s):  
Jun Huang ◽  
David Rowe ◽  
Wei Zhang ◽  
Tyler Suelter ◽  
Barbara Valent ◽  
...  
Keyword(s):  
Dna Repair ◽  
Dna Cleavage ◽  
Large Scale ◽  
Genome Engineering ◽  
Natural Populations ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Long Read ◽  
Repair Pathways

AbstractCRISPR-Cas mediated genome engineering has revolutionized functional genomics. However, basic questions remain regarding the mechanisms of DNA repair following Cas-mediated DNA cleavage. We developed CRISPR-Cas12a ribonucleoprotein genome editing in the fungal plant pathogen, Magnaporthe oryzae, and found frequent donor DNA integration despite the absence of long sequence homology. Interestingly, genotyping from hundreds of transformants showed that frequent non-canonical DNA repair outcomes predominated the recovered genome edited strains. Detailed analysis using sanger and nanopore long-read sequencing revealed five classes of DNA repair mutations, including single donor DNA insertions, concatemer donor DNA insertions, large DNA deletions, deletions plus donor DNA insertions, and infrequently we observed INDELs. Our results show that different error-prone DNA repair pathways resolved the Cas12a-mediated double-strand breaks (DSBs) based on the DNA sequence of edited strains. Furthermore, we found that the frequency of the different DNA repair outcomes varied across the genome, with some tested loci resulting in more frequent large-scale mutations. These results suggest that DNA repair pathways provide preferential repair across the genome that could create biased genome variation, which has significant implications for genome engineering and the genome evolution in natural populations.

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.

17α-ethynilestradiol and tributyltin mixtures modulates the expression of NER and p53 DNA repair pathways in male zebrafish gonads and disrupt offspring embryonic development

2018 ◽  
Vol 95 ◽  
pp. 1008-1018 ◽  
Author(s):  
Joana Soares ◽  
Teresa Neuparth ◽  
Angeliki Lyssimachou ◽  
Daniela Lima ◽  
Ana André ◽  
...  
Keyword(s):  
Dna Repair ◽  
Embryonic Development ◽  
Repair Pathways

Investigation on modulation of DNA repair pathways in Chinese MJD patients

2018 ◽  
Vol 71 ◽  
pp. 267.e5-267.e6 ◽  
Author(s):  
Chunrong Wang ◽  
Zhao Chen ◽  
Huirong Peng ◽  
Yun Peng ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Dna Repair ◽  
Repair Pathways

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

Analysis of representative mutants for key DNA repair pathways on healthspan in Caenorhabditis elegans

2021 ◽  
Vol 200 ◽  
pp. 111573
Author(s):  
Lucile Marchal ◽  
Shruthi Hamsanathan ◽  
Roshan Karthikappallil ◽  
Suhao Han ◽  
Himaly Shinglot ◽  
...  
Keyword(s):  
Dna Repair ◽  
Caenorhabditis Elegans ◽  
Repair Pathways
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