scholarly journals Mdt1 Facilitates Efficient Repair of Blocked DNA Double-Strand Breaks and Recombinational Maintenance of Telomeres

2007 ◽  
Vol 27 (18) ◽  
pp. 6532-6545 ◽  
Author(s):  
Brietta L. Pike ◽  
Jörg Heierhorst
Keyword(s):  
Dna Recombination ◽  
Double Strand Breaks ◽  
Telomere Maintenance ◽  
Type I ◽  
Dna Double Strand Breaks ◽  
Drug Induced ◽  
Exogenous Dna ◽  
Strand Breaks ◽  
Dramatic Shift ◽  
Recombination Pathway

ABSTRACT DNA recombination plays critical roles in DNA repair and alternative telomere maintenance. Here we show that absence of the SQ/TQ cluster domain-containing protein Mdt1 (Ybl051c) renders Saccharomyces cerevisiae particularly hypersensitive to bleomycin, a drug that causes 3′-phospho-glycolate-blocked DNA double-strand breaks (DSBs). mdt1Δ also hypersensitizes partially recombination-defective cells to camptothecin-induced 3′-phospho-tyrosyl protein-blocked DSBs. Remarkably, whereas mdt1Δ cells are unable to restore broken chromosomes after bleomycin treatment, they efficiently repair “clean” endonuclease-generated DSBs. Epistasis analyses indicate that MDT1 acts in the repair of bleomycin-induced DSBs by regulating the efficiency of the homologous recombination pathway as well as telomere-related functions of the KU complex. Moreover, mdt1Δ leads to severe synthetic growth defects with a deletion of the recombination facilitator and telomere-positioning factor gene CTF18 already in the absence of exogenous DNA damage. Importantly, mdt1Δ causes a dramatic shift from the usually prevalent type II to the less-efficient type I pathway of recombinational telomere maintenance in the absence of telomerase in liquid senescence assays. As telomeres resemble protein-blocked DSBs, the results indicate that Mdt1 acts in a novel blocked-end-specific recombination pathway that is required for the efficiency of both drug-induced DSB repair and telomerase-independent telomere maintenance.

scholarly journals Critical Role of RecN in Recombinational DNA Repair and Survival of Helicobacter pylori

2007 ◽  
Vol 76 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Ge Wang ◽  
Robert J. Maier
Keyword(s):  
Helicobacter Pylori ◽  
Parent Strain ◽  
Dna Recombination ◽  
Double Strand Breaks ◽  
Recombinational Repair ◽  
Wild Type ◽  
Dna Double Strand Breaks ◽  
Air Exposure ◽  
Strand Breaks ◽  
H Pylori

ABSTRACT Homologous recombination is one of the key mechanisms responsible for the repair of DNA double-strand breaks. Recombinational repair normally requires a battery of proteins, each with specific DNA recognition, strand transfer, resolution, or other functions. Helicobacter pylori lacks many of the proteins normally involved in the early stage (presynapsis) of recombinational repair, but it has a RecN homologue with an unclear function. A recN mutant strain of H. pylori was shown to be much more sensitive than its parent to mitomycin C, an agent predominantly causing DNA double-strand breaks. The recN strain was unable to survive exposure to either air or acid as well as the parent strain, and air exposure resulted in no viable recN cells recovered after 8 h. In oxidative stress conditions (i.e., air exposure), a recN strain accumulated significantly more damaged (multiply fragmented) DNA than the parent strain. To assess the DNA recombination abilities of strains, their transformation abilities were compared by separately monitoring transformation using H. pylori DNA fragments containing either a site-specific mutation (conferring rifampin resistance) or a large insertion (kanamycin resistance cassette). The transformation frequencies using the two types of DNA donor were 10- and 50-fold lower, respectively, for the recN strain than for the wild type, indicating that RecN plays an important role in facilitating DNA recombination. In two separate mouse colonization experiments, the recN strain colonized most of the stomachs, but the average number of recovered cells was 10-fold less for the mutant than for the parent strain (a statistically significant difference). Complementation of the recN strain by chromosomal insertion of a functional recN gene restored both the recombination frequency and mouse colonization ability to the wild-type levels. Thus, H. pylori RecN, as a component of DNA recombinational repair, plays a significant role in H. pylori survival in vivo.

scholarly journals Ku and the Stability of the Genome

2002 ◽  
Vol 2 (2) ◽  
pp. 61-65 ◽  
Author(s):  
Anna A. Friedl
Keyword(s):  
Double Strand Breaks ◽  
Telomere Maintenance ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Cellular Processes ◽  
Molecular Functions ◽  
Ku Proteins ◽  
The Stability ◽  
Dependent Processes

Ku proteins are associated with a variety of cellular processes such as repair of DNA-double-strand breaks, telomere maintenance and retrotransposition. In recent years, we have learned a lot about their cellular and molecular functions and it has turned out that Ku-dependent processes affect the stability of the genome, both positively and negatively, in several ways. This article gives an overview on the role of Ku in determining the shape of the genome.

scholarly journals DNA Double-Strand Breaks and Telomeres Play Important Roles in Trypanosoma brucei Antigenic Variation

2015 ◽  
Vol 14 (3) ◽  
pp. 196-205 ◽  
Author(s):  
Bibo Li
Keyword(s):  
Trypanosoma Brucei ◽  
Surface Antigen ◽  
Antigenic Variation ◽  
Dna Recombination ◽  
Double Strand Breaks ◽  
Microbial Pathogens ◽  
Dna Double Strand Breaks ◽  
Content Type ◽  
Strand Breaks ◽  
Major Surface

ABSTRACTHuman-infecting microbial pathogens all face a serious problem of elimination by the host immune response. Antigenic variation is an effective immune evasion mechanism where the pathogen regularly switches its major surface antigen. In many cases, the major surface antigen is encoded by genes from the same gene family, and its expression is strictly monoallelic. Among pathogens that undergo antigenic variation,Trypanosoma brucei(a kinetoplastid), which causes human African trypanosomiasis,Plasmodium falciparum(an apicomplexan), which causes malaria,Pneumocystis jirovecii(a fungus), which causes pneumonia, andBorrelia burgdorferi(a bacterium), which causes Lyme disease, also express their major surface antigens from loci next to the telomere. Except forPlasmodium, DNA recombination-mediated gene conversion is a major pathway for surface antigen switching in these pathogens. In the last decade, more sophisticated molecular and genetic tools have been developed inT. brucei, and our knowledge of functions of DNA recombination in antigenic variation has been greatly advanced. VSG is the major surface antigen inT. brucei. In subtelomeric VSG expression sites (ESs),VSGgenes invariably are flanked by a long stretch of upstream 70-bp repeats. Recent studies have shown that DNA double-strand breaks (DSBs), particularly those in 70-bp repeats in the active ES, are a natural potent trigger for antigenic variation inT. brucei. In addition, telomere proteins can influence VSG switching by reducing the DSB amount at subtelomeric regions. These findings will be summarized and their implications will be discussed in this review.

scholarly journals Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1

DNA Repair ◽  
2018 ◽  
Vol 63 ◽  
pp. 25-38 ◽  
Author(s):  
Fabrizia Carofiglio ◽  
Esther Sleddens-Linkels ◽  
Evelyne Wassenaar ◽  
Akiko Inagaki ◽  
Wiggert A. van Cappellen ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Exogenous Dna ◽  
Strand Breaks ◽  
Chromosome Synapsis

scholarly journals Rad51 stabilizes the ends of two adjacent DSBs in yeast

2019 ◽  
Vol 131 ◽  
pp. 01013
Author(s):  
Techang Chen ◽  
Xiaoqi Li ◽  
Ning Ma ◽  
Jingbo Shan ◽  
Peiyan Guo ◽  
...  
Keyword(s):  
Genomic Stability ◽  
Double Strand Breaks ◽  
Drop Out ◽  
Dna Double Strand Breaks ◽  
End Joining ◽  
Single Chromosome ◽  
Strand Breaks ◽  
Homologous Recombination Pathway ◽  
Non Homologous End Joining ◽  
Recombination Pathway

DNA double-strand breaks (DSBs) are a major form of DNA damage, and its accurate repair is critical for maintaining genomic stability and preventing cancer. Repair of DSBs is mainly through two pathways, homology-directed DNA repair (HDR) and non-homologous end joining (NHEJ). Compared with NHEJ, HDR has higher fidelity, so the study of interrelated factors in homologous recombination pathway is of particularly important. In this paper, we constructed an I-SceI model controlled by a galactose promoter that produces a DSB or two adjacent DSBs on a single chromosome. Rad50 and Rad51 genes are further deleted in these models. Sensitivity experiments show that Rad51 stabilizes the ends of two adjacent DSBs in yeast. Deletion of Rad51 gene causes the sequence between two adjacent DSBs to drop out directly to form a large gap. If this gap is larger, the efficiency of NHEJ will be greatly reduced, resulting in the deaths of the strain. Our research shows that Rad51 stabilizes the ends of two adjacent DSBs in yeast.

The repair of endo/exogenous DNA double-strand breaks and its effects on meiotic chromosome segregation in oocytes

2019 ◽  
Vol 28 (20) ◽  
pp. 3422-3430 ◽  
Author(s):  
Jun-Yu Ma ◽  
Xie Feng ◽  
Xin-Yi Tian ◽  
Lei-Ning Chen ◽  
Xiao-Yan Fan ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Chromosome ◽  
Genomic Structure ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Developmental Defects ◽  
Exogenous Dna ◽  
Strand Breaks ◽  
Dna Dsbs ◽  
Number Variation

Abstract Germ cell-derived genomic structure variants not only drive the evolution of species but also induce developmental defects in offspring. The genomic structure variants have different types, but most of them are originated from DNA double-strand breaks (DSBs). It is still not well known whether DNA DSBs exist in adult mammalian oocytes and how the growing and fully grown oocytes repair their DNA DSBs induced by endogenous or exogenous factors. In this study, we detected the endogenous DNA DSBs in the growing and fully grown mouse oocytes and found that the DNA DSBs mainly localized at the centromere-adjacent regions, which are also copy number variation hotspots. When the exogenous DNA DSBs were introduced by Etoposide, we found that Rad51-mediated homologous recombination (HR) was used to repair the broken DNA. However, the HR repair caused the chromatin intertwined and impaired the homologous chromosome segregation in oocytes. Although we had not detected the indication about HR repair of endogenous centromere-adjacent DNA DSBs, we found that Rad52 and RNA:DNA hybrids colocalized with these DNA DSBs, indicating that a Rad52-dependent DNA repair might exist in oocytes. In summary, our results not only demonstrated an association between endogenous DNA DSBs with genomic structure variants but also revealed one specific DNA DSB repair manner in oocytes.

scholarly journals DNA Double-Strand Breaks and DNA Recombination in Benzene Metabolite-Induced Genotoxicity

2012 ◽  
Vol 126 (2) ◽  
pp. 569-577 ◽  
Author(s):  
E. W. Y. Tung ◽  
N. A. Philbrook ◽  
K. D. D. MacDonald ◽  
L. M. Winn
Keyword(s):  
Dna Recombination ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks
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