Movatterモバイル変換


[0]ホーム

URL:


Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Full text links

Actions

Share

.2017 Apr 1;24(2):117-128.
doi: 10.1093/dnares/dsw059.

DNA double-strand break repair in Penaeus monodon is predominantly dependent on homologous recombination

Affiliations

DNA double-strand break repair in Penaeus monodon is predominantly dependent on homologous recombination

Shikha Srivastava et al. DNA Res..

Abstract

DNA double-strand breaks (DSBs) are mostly repaired by nonhomologous end joining (NHEJ) and homologous recombination (HR) in higher eukaryotes. In contrast, HR-mediated DSB repair is the major double-strand break repair pathway in lower order organisms such as bacteria and yeast. Penaeus monodon, commonly known as black tiger shrimp, is one of the economically important crustaceans facing large-scale mortality due to exposure to infectious diseases. The animals can also get exposed to chemical mutagens under the culture conditions as well as in wild. Although DSB repair mechanisms have been described in mammals and some invertebrates, its mechanism is unknown in the shrimp species. In the present study, we show that HR-mediated DSB repair is the predominant mode of repair in P. monodon. Robust repair was observed at a temperature of 30 °C, when 2 µg of cell-free extract derived from hepatopancreas was used for the study. Although HR occurred through both reciprocal recombination and gene conversion, the latter was predominant when the bacterial colonies containing recombinants were evaluated. Unlike mammals, NHEJ-mediated DSB repair was undetectable in P. monodon. However, we could detect evidence for an alternative mode of NHEJ that uses microhomology, termed as microhomology-mediated end joining (MMEJ). Interestingly, unlike HR, MMEJ was predominant at lower temperatures. Therefore, the results suggest that, while HR is major DSB repair pathway in shrimp, MMEJ also plays a role in ensuring the continuity and stability of the genome.

Keywords: Double-strand break; MMEJ; Microhomology; Nonhomologous DNA end joining; homologous recombination.

© The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Preparation of cell-free extract (CFE) of hepatopancreas of shrimp,P. monodon and evaluation of protein profile. (A) Image showing black tiger shrimp,Penaeus monodon. (B) Dorsal view of dissected out shrimp showing hepatopancreas.(C) Histological section of hepatopancreas showing the tubular architecture and different types of cells of hepatopancreatic tubules. (D) Schematic representation of steps involved in the preparation of cell-free extract from hepatopancreas ofP. monodon. (E) CBB staining showing protein profile of cell-free extracts of hepatopancreas. Different concentrations of CFE (5, 10, 15 µg) were resolved on a denaturing SDS-PAGE and stained with CBB stain.
Figure 2
Figure 2
Evaluation of compatible DNA end joining catalysed by extracts of hepatopancreas of shrimp. (A) Sequence of oligomeric DNA bearing 5′–5′ compatible ends used for the EJ study. (B, C) Evaluation of DNA end joining efficiency using increasing concentrations of CFE (0.01, 0.05, 0.1, 0.5, 1 and 2 µg) of hepatopancreas using 5′–5′ compatible end substrate (B) and in presence of additional cold oligomers (C). DNA incubated with rat testicular extract (RTE) was used as a positive control. Lane1 is no protein control and ‘M’ is 50 nt DNA ladder. Bar diagram showing quantitation of EJ efficiency along with the error bar (SEM). Intensity of the band was calculated and expressed in PSL units. Arrow indicates joined products; circular form I (monomer), linear dimer and circular form II (dimer) are shown.
Figure 3
Figure 3
Efficacy of end joining catalysed by extracts of hepatopancreas of shrimp, compared with oligomeric DNA bearing DSBs with different end structures. (A) Sequence of different oligomeric DNA substrates used for the NHEJ reaction. (B–E) Time kinetics of NHEJ catalysed by shrimp hepatopancreatic extracts (0.5 µg), when treated with 5′–5′ compatible end, (B) 5′–5′ noncompatible end (C), 5′–3′ noncompatible end (D) and blunt end (E) DNA substrates incubated for 2, 5, 15, 30 min and 1, 2 and 6 h. Products were resolved on denaturing PAGE. RTE treated samples served as positive control for respective type of DNA breaks. Lane 1 is no protein control and ‘M’ is 50 nt DNA ladder. In each panel, bar diagram displaying quantitation of NHEJ products is shown with error bar (SEM;n = 3). Joining products are indicated by arrow as circular form I (monomer), linear dimer and circular form II (dimer).
Figure 4
Figure 4
Evaluation of end joining catalysed by hepatopancreas extract of shrimp following radioactive PCR. (A) Different oligomeric DNA substrates (5′–5′ compatible, 5′–5′ noncompatible, 5′–3′ noncompatible and blunt end) were incubated with shrimp hepatopancreas CFE. The presence of end-joined products was examined through radioactive PCR. Amplified products were resolved on 8% denaturing PAGE. Lane 1, 4, 7, 10 are no protein control. Rat testicular extract treated samples served as positive controls. (B) Bar diagram displaying quantitation of joined products with error bar (SEM;n = 3) indicated. Band intensity was calculated and expressed in PSL units. Joined products are indicated by arrow. Multimers are shown in bracket. ‘M’ is 50 nt DNA ladder.
Figure 5
Figure 5
Efficiency of MMEJ catalysed by increasing concentrations of shrimp hepatopancreatic extract. (A) Schematic showing experimental strategy used for evaluating MMEJ in shrimp hepatopancreatic extract. Double-stranded oligomeric DNA possessing 10 nt microhomology region was used as DNA substrates as indicated and incubated with buffer and extracts at 30 °C for 2 h. Following termination of reaction, MMEJ products were amplified using radioactive PCR following labelling of one of the primers. PCR products were resolved on 8% denaturing PAGE and a characteristic 62 nt product indicates joining due to MMEJ. (B) DNA sequence of oligomers used for the study and 10 nt microhomology regions are indicated. (C) PAGE profile showing MMEJ products following incubation of DNA substrates with increasing concentrations of shrimp hepatopancreatic extracts (0.1, 0.25, 0.5, 1 and 2 µg). Lane 1 is no protein control and RTE treated sample was used as positive control. MMEJ product was indicated by arrow. (D) Bar diagram showing error bar (SEM;n = 3) based on the quantitation of multiple biological repeats of MMEJ reaction. The intensity of bands was calculated and expressed in PSL units. C-NHEJ products are shown in bracket. ‘M’ is 60 nt marker and ‘M’ is 50 nt DNA ladder.
Figure 6
Figure 6
Evaluation of MMEJ catalysed by hepatopancreatic extracts of shrimp at different incubation time and temperature. (A) PAGE profile showing time kinetics of MMEJ, when 10 nt microhomology DNA substrate was used. Shrimp hepatopancreatic extracts (0.5 µg) were incubated at 30 °C for different time points (2, 5, 15, 30 min, 1, 2, 6 h). (B) Bar diagram with error bar (SEM) showing quantitation of MMEJ products at different time points (n = 3). (C) PAGE profile showing efficiency of MMEJ catalysed by extracts of shrimp hepatopancreas (0.5 µg) at different temperature (4, 16, 25, 30 and 37 °C) incubated for 2 h. (D) Bar diagram showing error bar (SEM) of MMEJ products at different temperature (n = 3). C-NHEJ products are shown in bracket. ‘M’ is 60 nt marker and ‘M’ is 50 nt DNA ladder.
Figure 7
Figure 7
Evaluation of HR-mediated DSB repair catalysed by hepatopancreas extracts. (A) Schematic presentation showing plasmid based HR assay. Plasmids (pTO223 and pTO231) were incubated with shrimp hepatopancreas CFE in HR assay buffer at 30 °C for 30 min. Purified DNA was used for transformation ofE. coli DH5α and plated on agar plates containing ampicillin to determine transformation efficiency and kanamycin to calculate recombination frequency. (B) Table showingin vitro recombination catalysed by hepatopancreas extract and its heat inactivated form. Mouse testicular extracts acted as a positive control. (C) Efficacy of HR-mediated DSB repair in shrimp hepatopancreatic extract when examined at different incubation temperatures. Hepatopancreatic extracts (0.5 µg) were incubated with substrate DNA at different temperature (4, 16, 24, 30, 37 °C). (D) Bar diagram showing recombination frequencies catalysed by increasing concentrations (0.5, 1, 1.5, 2, 4 µg) of shrimp hepatopancreas extract. ‘C’ is no protein control.
Figure 8
Figure 8
Evaluation of molecular mechanism of HR-mediated DSB repair in hepatopancreatic extract of shrimp. (A) Schematics showing reciprocal recombination and gene conversion-mediated HR that can lead to recreation of functionalneo gene.neoΔ1 in pTO231 andneoΔ2 in pTO223 are nonfunctionalneomycin genes.neoΔ1 lacksNaeI towards right side of the gene (shown in red) andneoΔ2 lacksNarI towards the left side of the gene (shown in red). A crossing over between two mutants will give rise to a functionalneo gene and a nonfunctional allele containing both the deletions. In the case of gene conversion, transfer of DNA fromneoΔ1 toneoΔ2 takes place resulting in functionalneo gene.HindIII site present adjacent toEcoRI site was destroyed inneoΔ1, henceHindIII/SalI resulting in 1.5 kb fragment occurs only at the time of gene conversion. (B) Representative agarose gel profile showingEcoRI/SalI restriction digestion of recombinant clones. Lanes 1–7 show release of fragment size of 1.5 kb of functionalneo gene; 223 and 231 are mutant plasmids. (C) Agarose gel profile showingHindIII/SalI restriction digestion of recombinants. Lanes 1–7 show gene conversion releasing 1.5 kb of functionalneo gene, except in the case of lane 4. Lane 3 showed a partially digested clone. ‘M’ is 1 kb DNA ladder. (D) Bar diagram showing frequency of HR-mediated DSB repair through either gene conversion or reciprocal recombination.
Figure 9
Figure 9
Cartoon depicting comparison of major DSB repair pathways in mammals andPenaeus monodon. Unlike mammals, HR and alternative NHEJ (MMEJ) are the major DNA break repair pathways in shrimp. Classical NHEJ and HR are the major DSB repair pathways in mammals, while MMEJ operates only at a low level.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Srivastava M., Raghavan S.C.. 2015, DNA double-strand break repair inhibitors as cancer therapeutics. Chem. Biol., 22, 17–29. - PubMed
    1. Friedberg E.C., Aguilera A., Gellert M., et al. 2006, DNA repair: from molecular mechanism to human disease. DNA Repair, 5, 986–96. - PubMed
    1. Friedberg E.C., Backendorf C., Burke J., et al. 1987, Molecular aspects of DNA repair. Mutation Res, 184, 67–86. - PubMed
    1. Nambiar M., Raghavan S.C.. 2013, Chromosomal translocations among the healthy human population: implications in oncogenesis. Cell. Mol. Life Sci, 70, 1381–92. - PMC - PubMed
    1. Sharma S., Raghavan S.C.. 2010, Nonhomologous DNA end joining in cell-free extracts. J. Nucleic Acids. - PMC - PubMed

MeSH terms

Substances

Related information

LinkOut - more resources

Full text links
Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.


[8]ページ先頭

©2009-2025 Movatter.jp