scholarly journals Search for Genes Essential for Pneumococcal Transformation: the RadA DNA Repair Protein Plays a Role in Genomic Recombination of Donor DNA

2007 ◽  
Vol 189 (18) ◽  
pp. 6540-6550 ◽  
Author(s):  
Peter Burghout ◽  
Hester J. Bootsma ◽  
Tomas G. Kloosterman ◽  
Jetta J. E. Bijlsma ◽  
Christa E. de Jongh ◽  
...  
Keyword(s):  
Dna Repair ◽  
Response Regulator ◽  
Selection Strategy ◽  
Gene Encoding ◽  
Damage Repair ◽  
Repair Protein ◽  
Genomic Array ◽  
Dna Repair Protein ◽  
Increased Sensitivity ◽  
Genomic Recombination

ABSTRACT We applied a novel negative selection strategy called genomic array footprinting (GAF) to identify genes required for genetic transformation of the gram-positive bacterium Streptococcus pneumoniae. Genome-wide mariner transposon mutant libraries in S. pneumoniae strain R6 were challenged by transformation with an antibiotic resistance cassette and growth in the presence of the corresponding antibiotic. The GAF screen identified the enrichment of mutants in two genes, i.e., hexA and hexB, and the counterselection of mutants in 21 different genes during the challenge. Eight of the counterselected genes were known to be essential for pneumococcal transformation. Four other genes, i.e., radA, comGF, parB, and spr2011, have previously been linked to the competence regulon, and one, spr2014, was located adjacent to the essential competence gene comFA. Directed mutants of seven of the eight remaining genes, i.e., spr0459-spr0460, spr0777, spr0838, spr1259-spr1260, and spr1357, resulted in reduced, albeit modest, transformation rates. No connection to pneumococcal transformation could be made for the eighth gene, which encodes the response regulator RR03. We further demonstrated that the gene encoding the putative DNA repair protein RadA is required for efficient transformation with chromosomal markers, whereas transformation with replicating plasmid DNA was not significantly affected. The radA mutant also displayed an increased sensitivity to treatment with the DNA-damaging agent methyl methanesulfonate. Hence, RadA is considered to have a role in recombination of donor DNA and in DNA damage repair in S. pneumoniae.

scholarly journals ATM controls DNA repair and mitochondria transfer between neighboring cells

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Sha Jin ◽  
Nils Cordes
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dependent Manner ◽  
Intercellular Signaling ◽  
Tissue Integrity ◽  
Damage Repair ◽  
Repair Protein ◽  
Mitochondria Transfer ◽  
Dna Repair Protein ◽  
Direct Cell

Abstract Intercellular communication is essential for multicellular tissue vitality and homeostasis. We show that healthy cells message protective signals through direct cell–cell connections to adjacent DNA–damaged cells in a microtubule–dependent manner. In DNA–damaged cells, mitochondria restoration is facilitated by fusion with undamaged mitochondria from healthy cells and their DNA damage repair is optimized in presence of healthy cells. Both, mitochondria transfer and intercellular signaling for an enhanced DNA damage response are critically regulated by the activity of the DNA repair protein ataxia telangiectasia mutated (ATM). These healthy–to–damaged prosurvival processes sustain normal tissue integrity and may be exploitable for overcoming resistance to therapy in diseases such as cancer.

BCR-ABL down-regulates the DNA repair protein DNA-PKcs

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 2084-2090 ◽  
Author(s):  
Eric Deutsch ◽  
Aymeric Dugray ◽  
Bassam AbdulKarim ◽  
Elisabetta Marangoni ◽  
Laurence Maggiorella ◽  
...  
Keyword(s):  
Dna Repair ◽  
Blast Crisis ◽  
Genetic Alterations ◽  
Myelogenous Leukemia ◽  
Down Regulation ◽  
Repair Deficiency ◽  
Repair Protein ◽  
Dna Repair Deficiency ◽  
Dna Repair Protein ◽  
Increased Sensitivity

Abstract This study demonstrates in both stable and inducible BCR-ABL–expressing hematopoietic cells a down-regulation of the major mammalian DNA repair protein DNA-PKcs by BCR-ABL. Similar results were found in BCR-ABL CD34+ cells from patients with chronic myelogenous leukemia (CML). DNA-PKcs down-regulation is a proteasome-dependent degradation that requires tyrosine kinase activity and is associated with a marked DNA repair deficiency along with increased sensitivity to ionizing radiation. The conjunction of a major DNA repair deficiency and a resistance to apoptosis, both induced by BCR-ABL, provides a new mechanism to explain how secondary genetic alterations can accumulate in CML, eventually leading to blast crisis. The down-regulation of DNA-PKcs was reversible in CD34+ CML cells suggesting that this approach might offer a novel and powerful therapeutic strategy in this disease, especially to delay the blast crisis.

scholarly journals A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M

2005 ◽  
Vol 37 (9) ◽  
pp. 958-963 ◽  
Author(s):  
Amom Ruhikanta Meetei ◽  
Annette L Medhurst ◽  
Chen Ling ◽  
Yutong Xue ◽  
Thiyam Ramsing Singh ◽  
...  
Keyword(s):  
Dna Repair ◽  
Fanconi Anemia ◽  
Complementation Group ◽  
Repair Protein ◽  
Dna Repair Protein ◽  
Human Ortholog

Chemoproteomics-Enabled Discovery of a Potent and Selective Inhibitor of the DNA Repair Protein MGMT

2016 ◽  
Vol 55 (8) ◽  
pp. 2911-2915 ◽  
Author(s):  
Chao Wang ◽  
Daniel Abegg ◽  
Dominic G. Hoch ◽  
Alexander Adibekian
Keyword(s):  
Dna Repair ◽  
Selective Inhibitor ◽  
Repair Protein ◽  
Dna Repair Protein

Partial characterization of the DNA repair protein complex, containing the ERCC1, ERCC4, ERCC11 and XPF correcting activities

1995 ◽  
Vol 337 (1) ◽  
pp. 25-39 ◽  
Author(s):  
A.J. van Vuuren ◽  
E. Appeldoorn ◽  
H. Odijk ◽  
S. Humbert ◽  
V. Moncollin ◽  
...  
Keyword(s):  
Dna Repair ◽  
Protein Complex ◽  
Partial Characterization ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals ROS induces NETosis by oxidizing DNA and initiating DNA repair

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dhia Azzouz ◽  
Meraj A. Khan ◽  
Nades Palaniyar
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Polymerase Activity ◽  
Neutrophil Activation ◽  
Neutrophil Extracellular Trap ◽  
Nuclear Antigen ◽  
Chromatin Decondensation ◽  
Genome Wide ◽  
Repair Protein ◽  
Dna Repair Protein

AbstractReactive oxygen species (ROS) are essential for neutrophil extracellular trap (NET) formation or NETosis. Nevertheless, how ROS induces NETosis is unknown. Neutrophil activation induces excess ROS production and a meaningless genome-wide transcription to facilitate chromatin decondensation. Here we show that the induction of NADPH oxidase-dependent NETosis leads to extensive DNA damage, and the subsequent translocation of proliferating cell nuclear antigen (PCNA), a key DNA repair protein, stored in the cytoplasm into the nucleus. During the activation of NETosis (e.g., by phorbol myristate acetate, Escherichia coli LPS, Staphylococcus aureus (RN4220), or Pseudomonas aeruginosa), preventing the DNA-repair-complex assembly leading to nick formation that decondenses chromatin causes the suppression of NETosis (e.g., by inhibitors to, or knockdown of, Apurinic endonuclease APE1, poly ADP ribose polymerase PARP, and DNA ligase). The remaining repair steps involving polymerase activity and PCNA interactions with DNA polymerases β/δ do not suppress agonist-induced NETosis. Therefore, excess ROS produced during neutrophil activation induces NETosis by inducing extensive DNA damage (e.g., oxidising guanine to 8-oxoguanine), and the subsequent DNA repair pathway, leading to chromatin decondensation.

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