The first document discusses two studies: 1) a study investigating the role of the TopBP1 protein in DNA damage response and the ATR-Chk1 checkpoint pathway in Xenopus egg extracts, finding that Importin β transports TopBP1 into the nucleus and this transport plays a role in checkpoint signaling, and 2) a study examining the evolution of the cellular immune response against parasitoids in 11 Drosophila species through phenotypic and genomic analysis, finding gene families associated with gains and losses of resistance. The second document provides context about the student and their analysis of the medical relevance of these two studies, noting their potential contributions to personalized cancer treatment and pharmacogenetics.

1. 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 Navarro
Medicine student
III Semester
UPB

2. BIBLIOGRAPHY
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.
•
•
Importin
β-dependent
nuclear import of TopBP1 in
ATR–Chk1 checkpoint in
Xenopus
egg
extracts.
January 9, 2014.
From:
www.elsevier.com/locate/cell
sig.
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–Chk1
checkpoint in Xenopus egg
extracts and Evolution of a cellular
immune response in Drosophila:
a phenotypic and genomic
comparative analysis.
Virginia Espinosa
Navarro
Medical student
III semester
UPB
Teacher
Lina Martínez

3. INTRODUCTION
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.
Importin β-dependent nuclear
import of TopBP1 in ATR–Chk1
checkpoint in Xenopus egg
extracts
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.
Evolution of a cellular
immune response in
Drosophila:
a phenotypic and genomic
comparative analysis
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.

4. 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. .

6. MATERIALS AND METHODS
Xenopus
egg
extract
preparation and
related procedures
Recombinant
proteins and
antibodies
Coimmunoprecipitation
(Co-IP) assays
Immunofluorescence
microscopy
GST pulldown assays

7. RESULTS
Importin β interacts
with TopBP1
The CTM motif of TopBP1
mediates its interaction
with Importin β
The CTM motif of
TopBP1
is
required
for
nuclear
import
from outside of
assembled nuclei.
The CT100 fragment of
Importin β is required for
TopBP1 association

8. RESULTS
Importin
β-specific
inhibitor importazole
compromised
the
nuclear
import
of
TopBP1
Nuclear import of
TopBP1 plays a distinct
regulatory role in the
DNA
damage
response
The
CTM-dependent
nuclear import of TopBP1 is
required for ATR–Chk1
checkpoint signaling, not
due to its requirement for
DNA replication

9. 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.

11. MATERIALS AND METHODS
Species
strains
Encapsulation
assay
Melanization
Candidate
genes
Lamellocyte
identification

12. MATERIALS AND METHODS
Orthologous
groups and
homology
categories
Phylogenetic
analysis
Immune
classification
Positive
selection
RT-qPCR

13. RESULTS
Phenotypic characterization:
Only
species
of
the
melanogaster subgroup show
encapsulation
ability
and
produce lamellocytes
Comparative Genomics
Orthologs
Comparative expression of TepI,
PPO3 and IM1
Lineage specic gains and losses
Sequence divergence

15. 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.

16. 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,.

17. 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.

18. 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

19. 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/.