presentación biología molecular
TRANSCRIPT
Importin β-dependent nuclear import of TopBP1 in ATR–Chk1
checkpoint in Xenopus egg extracts and Evolution of a
cellular immune response in Drosophila:
a phenotypic and genomic comparative analysis.
Virginia Espinosa NavarroMedicine student
III SemesterUPB
Virginia Espinosa NavarroMedicine student
III SemesterUPB
BIBLIOGRAPHY
• Importin β-dependent nuclear import of TopBP1 in ATR–Chk1 checkpoint in Xenopus egg extracts. January 9, 2014. From: www.elsevier.com/locate/cellsig.
• Evolution of a cellular immune response in Drosophila: a phenotypic and genomic comparative analysis. Janyary 18, 2014. From: http://gbe.oxfordjournals.org/.
Importin β-dependent nuclear import of TopBP1 in
ATR–Chk1checkpoint in Xenopus egg extracts and Evolution of a
cellular immune response in Drosophila:
a phenotypic and genomic comparative analysis.
Teacher Lina Martínez
Virginia Espinosa Navarro
Medical studentIII semester
UPB
MEDICAL
UTILITY
This first study is of great clinical importance because, genetic and molecular biological studies offer us a path toward personalized treatment and prognostic factors, one of which includes the prevention of breast cancer, and it is known that family susceptibility to breast cancer comprises 25% of all breast tumors, so the ratio of the TopBP1 protein susceptibility to breast cancer is a step that leads us to find an appropriate and effective prevention.In the second study, the clinical importance of the phenotypic and genomic analysis comes from the possibility that the drug therapy can be safer and more effective when the genotype of the patient is known. Pharmacogenetic studies can be considered studies of interaction between genes and environment, considering pharmacological treatment as an environmental variable.
INTRODUCTIONImportin β-dependent
nuclear import of TopBP1 in ATR–Chk1
checkpoint in Xenopus egg extracts
Evolution of a cellular immune response in
Drosophila:a phenotypic and
genomic comparative analysis
In the first article, we seek to clarify one of the aspects that influence the susceptibility to breast cancer, and it’s importing the TopBP1 protein from the nucleus to the cytoplasm. Taking advantage of the cell-free Xenopus egg extract system, was investigated the roles of TopBP1 in DNA metabolism including DNA replication and DDR through a series of studies And all these data suggest that the Importin β-dependent shuttling of TopBP1 into nucleus plays an important role in the ATR–Chk1 checkpoint signaling in Xenopus.
At the second one, the propose that they had with the article was investigate the large interspecific differences in the ability to survive infection by parasitoids, across 11 Drosophila species and identify genomic changes associated with the evolution of cellular immunity in the Drosophila genu and the gains and losses of parasitoid resistance.
By identifying the importance of having the TopBP1 protein in DNA metabolism, replication, damage response and transcriptional regulation, and besides that, it has been identified that its location is associated with susceptibility to breast cancer , they wanted to do this study to investigate the way this core protein is transported to the cytoplasm, and a protein that interacted with TopBP1 C-terminal, known as B importin was found. After a series of procedures, managed to conclude important facts such as: Importin β has been identified as a new interacting protein of TopBP1 C-terminus.•A C-terminal motif in TopBP1 is important for its nuclear import.•Importazole inhibits TopBP1's nuclear import and ATR–Chk1 checkpoint signaling.•With ongoing DNA replication, nuclear import of TopBP1 is required for checkpoint.•Checkpoint activation requires more TopBP1 than DNA replication does.
As well the name says , this article seeks to evaluate the evolution of the immune response by phenotypic and genotypic comparison, for that, was investigated the large interspecific differences in the ability to survive infection by parasitoids across 11 Drosophila species and identify genomic changes associated with gains and losses of parasitoid resistance. They provide an important step towards understanding the evolution of the cellular resistance against parasitoids in Drosophila species and they showed that a combination of cooption and neofunctionalization is likely to have contributed to the acquiring of the new immunity component in the cellular immune response, and that particular gene families (serine-type proteases, Teps and lectins ) could be of special interest for the processes of hemocyte differentiation, proliferation and activation.
The susceptibility to breast cancer comprises 25% of all breast tumors, and the importing the TopBP1 protein from the nucleus to the cytoplasm plays an important role in this. Taking advantage of the cell-free Xenopus egg extract system, was investigated the roles of TopBP1 in DNA metabolism including DNA replication and DDR through a series of studies And all these data suggest that the Importin β-dependent shuttling of TopBP1 into nucleus plays an important role in the ATR–Chk1 checkpoint signaling in Xenopus.
The study about the evolution of a cellular immune response in Drosophila, show us that through a combination of phenotypic and genomic characterizations , they provide an important step towards understanding the evolution of the cellular resistance against parasitoids in Drosophila species. .
INT
RO
DU
CT
ION
Importin â-dependent nuclear import of TopBP1 in ATR–Chk1
checkpoint in Xenopus egg extracts
Xenopus egg extract preparation and related procedures
Recombinant proteins and antibodies
GST pulldown assays
Coimmunoprecipitation (Co-IP) assays
Immunofluorescence microscopy
MATERIALS AND METHODS
Importin β interacts with TopBP1
The CTM motif of TopBP1 mediates its interaction with Importin β
The CT100 fragment of Importin β is required for TopBP1 association
The CTM motif of TopBP1 is required for nuclear import from outside of assembled nuclei.
RESULTS
Importin β-specific inhibitor importazole compromised the nuclear import of TopBP1
The CTM-dependent nuclear import of TopBP1 is required for ATR–Chk1 checkpoint signaling, not due to its requirement for DNA replication
Nuclear import of TopBP1 plays a distinct regulatory role in the DNA damage response
RESULTS
OBSERVATION
Breast cancer is a reality that affects all women, and all of which are likely to have, it is vital to attend these studies, where molecular biology gives us significant events that influence the disease. In my opinion it is an article of great interest and it brings a lot to the medical science, indicating the influence of the TopBP1 protein in breast cancer susceptibility.
Evolution of a cellular immune response in
Drosophila:a phenotypic and genomic
comparative analysis
Species strains
Encapsulation assay
Lamellocyte identification
Melanization
Candidate genes
MATERIALS AND METHODS
Phylogenetic analysis
Immune classification
Positive selection
RT-qPCR
Orthologous groups and homology categories
MATERIALS AND METHODS
Phenotypic characterization: Only species of the melanogaster subgroup showencapsulation ability and produce lamellocytes
Comparative Genomics
Orthologs
Lineage specic gains and losses
Sequence divergence
Comparative expression of TepI, PPO3 and IM1
RESULTS
OBSERVATION
In this studio, they provide an important step towards understanding the evolution of the cellular resistance against parasitoids in Drosophila species, that’s important because, It has been argued that it may be beneficial to the public health use genetic information to stratify the allocation of environmental settings that prevent disease, although this view is not universally accepted.
MEDICAL
UTILITY
This first study is of great clinical importance because, genetic and molecular biological studies offer us a path toward personalized treatment and prognostic factors, one of which includes the prevention of breast cancer,.
MEDICAL
UTILITY
it is known that family susceptibility to breast cancer comprises 25% of all breast tumors, so the ratio of the TopBP1 protein susceptibility to breast cancer is a step that leads us to find an appropriate and effective prevention.
MEDICAL
UTILITY
In the second study, the clinical importance of the phenotypic and genomic analysis comes from the possibility that the drug therapy can be safer and more effective when the genotype of the patient is known. Pharmacogenetic studies can be considered studies of interaction between genes and environment, considering pharmacological treatment as an environmental variable
BIBLIOGRAPHY
• Importin β-dependent nuclear import of TopBP1 in ATR–Chk1 checkpoint in Xenopus egg extracts. January 9, 2014. From: www.elsevier.com/locate/cellsig.
• Evolution of a cellular immune response in Drosophila: a phenotypic and genomic comparative analysis. Janyary 18, 2014. From: http://gbe.oxfordjournals.org/.