DSB (Im)mobility and DNA Repair Compartmentalization in Mammalian Cells

2015 ◽  
Vol 427 (3) ◽  
pp. 652-658 ◽  
Author(s):  
Charlène Lemaître ◽  
Evi Soutoglou
Keyword(s):  
Dna Repair ◽  
Mammalian Cells

scholarly journals Exploiting DNA Endonucleases to Advance Mechanisms of DNA Repair

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 530
Author(s):  
Marlo K. Thompson ◽  
Robert W. Sobol ◽  
Aishwarya Prakash
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Genome Stability ◽  
Gene Editing ◽  
Adaptive Immune System ◽  
Zinc Finger Nucleases ◽  
Specific Gene ◽  
Target Sequence ◽  
Transcription Activator ◽  
Low Cytotoxicity

The earliest methods of genome editing, such as zinc-finger nucleases (ZFN) and transcription activator-like effector nucleases (TALENs), utilize customizable DNA-binding motifs to target the genome at specific loci. While these approaches provided sequence-specific gene-editing capacity, the laborious process of designing and synthesizing recombinant nucleases to recognize a specific target sequence, combined with limited target choices and poor editing efficiency, ultimately minimized the broad utility of these systems. The discovery of clustered regularly interspaced short palindromic repeat sequences (CRISPR) in Escherichia coli dates to 1987, yet it was another 20 years before CRISPR and the CRISPR-associated (Cas) proteins were identified as part of the microbial adaptive immune system, by targeting phage DNA, to fight bacteriophage reinfection. By 2013, CRISPR/Cas9 systems had been engineered to allow gene editing in mammalian cells. The ease of design, low cytotoxicity, and increased efficiency have made CRISPR/Cas9 and its related systems the designer nucleases of choice for many. In this review, we discuss the various CRISPR systems and their broad utility in genome manipulation. We will explore how CRISPR-controlled modifications have advanced our understanding of the mechanisms of genome stability, using the modulation of DNA repair genes as examples.

scholarly journals An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III.

1994 ◽  
Vol 14 (1) ◽  
pp. 68-76 ◽  
Author(s):  
K W Caldecott ◽  
C K McKeown ◽  
J D Tucker ◽  
S Ljungquist ◽  
L H Thompson
Keyword(s):  
Dna Repair ◽  
Affinity Chromatography ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Affinity Purification ◽  
Alkylating Agents ◽  
Chinese Hamster ◽  
Dna Ligase ◽  
Base Excision ◽  
Dna Ligase Iii

XRCC1, the human gene that fully corrects the Chinese hamster ovary DNA repair mutant EM9, encodes a protein involved in the rejoining of DNA single-strand breaks that arise following treatment with alkylating agents or ionizing radiation. In this study, a cDNA minigene encoding oligohistidine-tagged XRCC1 was constructed to facilitate affinity purification of the recombinant protein. This construct, designated pcD2EHX, fully corrected the EM9 phenotype of high sister chromatid exchange, indicating that the histidine tag was not detrimental to XRCC1 activity. Affinity chromatography of extract from EM9 cells transfected with pcD2EHX resulted in the copurification of histidine-tagged XRCC1 and DNA ligase III activity. Neither XRCC1 or DNA ligase III activity was purified during affinity chromatography of extract from EM9 cells transfected with pcD2EX, a cDNA minigene that encodes untagged XRCC1, or extract from wild-type AA8 or untransfected EM9 cells. The copurification of DNA ligase III activity with histidine-tagged XRCC1 suggests that the two proteins are present in the cell as a complex. Furthermore, DNA ligase III activity was present at lower levels in EM9 cells than in AA8 cells and was returned to normal levels in EM9 cells transfected with pcD2EHX or pcD2EX. These findings indicate that XRCC1 is required for normal levels of DNA ligase III activity, and they implicate a major role for this DNA ligase in DNA base excision repair in mammalian cells.

DNA Repair in Mammalian Cells

2009 ◽  
Vol 66 (6) ◽  
pp. 1010-1020 ◽  
Author(s):  
S. Tornaletti
Keyword(s):  
Dna Repair ◽  
Mammalian Cells

DNA Repair Genes of Mammalian Cells

1986 ◽  
pp. 349-358 ◽  
Author(s):  
L. H. Thompson ◽  
K. W. Brookman ◽  
E. P. Salazar ◽  
J. C. Fuscoe ◽  
C. A. Weber
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Dna Repair Genes ◽  
Repair Genes

DNA Repair Enzymes in Mammalian Cells

1977 ◽  
pp. 263-322 ◽  
Author(s):  
Errol C. Friedberg ◽  
Kern H. Cook ◽  
James Duncan ◽  
Kristien Mortelmans
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Dna Repair Enzymes ◽  
Repair Enzymes

Chemical carcinogens

2019 ◽  
pp. 79-90
Author(s):  
David H. Phillips
Keyword(s):  
Dna Repair ◽  
Cancer Incidence ◽  
Mammalian Cells ◽  
Human Exposure ◽  
Chemical Carcinogens ◽  
Regulatory Processes ◽  
Genotoxic Carcinogens ◽  
The Many ◽  
Transformation Methods ◽  
Insight Into

Large geographical and temporal differences in cancer incidence indicate that the causes of the majority of cases are a consequence of environmental and lifestyle factors. While many of these remain unknown, around half have known causes, and these include chemicals in air, water, and food, as well as products of industrial processes and of combustion. The major classes of chemical carcinogens and how they were discovered are described. A property shared by many of them is that they, or one or more of their metabolites, are electrophiles that can damage DNA in mammalian cells, leading to cellular responses including DNA repair, cytotoxicity, apoptosis, mutagenesis, and malignant transformation. Methods for predicting the carcinogenicity of new chemicals are part of the regulatory processes for safety assessment, and sensitive methods for monitoring human exposure to carcinogens provide insight into the aetiology of cancer. The mutational signatures that genotoxic carcinogens leave in the tumours they induce provide evidence of the chemicals that have caused them, and the approach has promise for shedding light on the many as-yet-unidentified cases of cancer worldwide.

scholarly journals A yeast DNA repair gene partially complements defective excision repair in mammalian cells.

1988 ◽  
Vol 7 (10) ◽  
pp. 3245-3253 ◽  
Author(s):  
C. Lambert ◽  
L. B. Couto ◽  
W. A. Weiss ◽  
R. A. Schultz ◽  
L. H. Thompson ◽  
...  
Keyword(s):  
Dna Repair ◽  
Mammalian Cells ◽  
Excision Repair ◽  
Repair Gene ◽  
Dna Repair Gene
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