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Papers by Jean-Patrick Pommier
arXiv (Cornell University), Dec 20, 2017
In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and ... more In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and biomedical research. Unfortunately, chromosomes often overlap and it is necessary to identify and distinguish between the overlapping chromosomes. A segmentation solution that is fast and automated will enable scaling of cost effective medicine and biomedical research. We apply neural network-based image segmentation to the problem of distinguishing between partially overlapping DNA chromosomes. A convolutional neural network is customized for this problem. The results achieved intersection over union (IOU) scores of 94.7% for the overlapping region and 88-94% on the non-overlapping chromosome regions.
Molecular and Cellular Biology, May 1, 2002
We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To ... more We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To this end, we established telomerase-positive cell lines in which the targeting of these telomeric proteins to specific telomeres could be induced. We demonstrate that their targeting leads to telomere shortening. This indicates that these proteins act in cis to repress telomere elongation. Inhibition of telomerase activity by a modified oligonucleotide did not further increase the pace of telomere erosion caused by TRF1 targeting, suggesting that telomerase itself is the target of TRF1 regulation. In contrast, TRF2 targeting and telomerase inhibition have additive effects. The possibility that TRF2 can activate a telomeric degradation pathway was directly tested in human primary cells that do not express telomerase. In these cells, overexpression of full-length TRF2 leads to an increased rate of telomere shortening.
Biochimie, 1995
The very end of the chromosome is called the telomere and is composed of DNA repeat sequences and... more The very end of the chromosome is called the telomere and is composed of DNA repeat sequences and associated proteins. Genetic and biochemical analyses of this complex, the telosome, lead to the hypothesis that transcription and DnA replication are submitted to position effects mediated by the telomere proximity. Telomere lengthr reduction and alterations of the telomeric chromatin assembly might explain the chromosome instability which occurs during the senescence and the immortalization process in vitro. A particular polymerase, the telomerase, is able to lengthen the telomeres. A telomerase activity was characterized in yeast, Tetrahymena, but also in transformed and in germline cells. We reviewed the involvement of telomeres in the aging process. We proposed that the short size of the telomere repeat at each chromosome could direct the loss of heterozygosity, t hus telomere length could play a role in individual and tissular susceptibility to develop cancer. Antitelomerase strategy for cancer therapy is attractive but limited by the short decrease of the telomere lenght at each cell division.
Biology of the Cell, Sep 1, 1999
Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been ... more Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been generally assumed that activation of telomerase prevents further telomere shortening and is essential for cell immortalization. In this study, we performed a detailed cytogenetic ...
ArXiv, 2017
In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and ... more In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and biomedical research. Unfortunately, chromosomes often overlap and it is necessary to identify and distinguish between the overlapping chromosomes. A segmentation solution that is fast and automated will enable scaling of cost effective medicine and biomedical research. We apply neural network-based image segmentation to the problem of distinguishing between partially overlapping DNA chromosomes. A convolutional neural network is customized for this problem. The results achieved intersection over union (IOU) scores of 94.7% for the overlapping region and 88-94% on the non-overlapping chromosome regions.
Les telomeres sont des complexes nucleoproteiques localises a l'extremite des chromosomes euc... more Les telomeres sont des complexes nucleoproteiques localises a l'extremite des chromosomes eucaryotes. Les telomeres protegent les chromosomes d'une perte d'informations genetiques. Les motifs telomeriques (ttaggg)n etre restaures apres elongation par la telomerase. L'activite telomerase est faible ou absente dans les cellules somatiques cyclantes qui possedent un potentiel de division limite, tandis que les cellules immortelles, comme les cellules de la lignee germinale ou les cellules tumorales ont une activite elevee. Nous avons ameliores et concu de nouvelles techniques pour analyser la longueur des telomeres par southern-blot et par hybridation in-situ. La distribution de la longueur des telomeres a ete analysee dans des fibroblastes primaires jusqu'a la senescence, dans ces memes fibroblastes apres transformation par sv40 et dans des lymphocytes de patients vih +. Chez les patients vih+ avec moins de 200 t4 par mm3, on detecte une diminution de la longueur d...
Methods in molecular biology (Clifton, N.J.), 2002
ABSTRACT
Virology, 1997
Telomeres are complex protein-DNA structures located at the ends of eukaryotic chromosomes. In a ... more Telomeres are complex protein-DNA structures located at the ends of eukaryotic chromosomes. In a normal cell, telomere DNA shortens with cell divisions. Such a telomere loss may act as a mitotic clock to eventually signal cell cycling exit and cellular senescence. In a transversal study, we found a marked decrease in telomere length of peripheral blood mononuclear cells in HIV-infected patients with advanced immunodeficiency. This telomere reduction concerns T4, T8, and B lymphocytes, providing evidence of high turnover of these cells in the course of HIV infection. These data suggest that replicative senescence could be involved in the final immunosuppression and may have important therapeutical implications. ᭧ 1997 Academic Press these mechanisms remain poorly known, although an-148
Biology of the Cell, 1999
Biology of The Cell, 1999
Virology, 1997
Telomeres are complex protein–DNA structures located at the ends of eukaryotic chromosomes. In a ... more Telomeres are complex protein–DNA structures located at the ends of eukaryotic chromosomes. In a normal cell, telomere DNA shortens with cell divisions. Such a telomere loss may act as a mitotic clock to eventually signal cell cycling exit and cellular senescence. In a transversal study, we found a marked decrease in telomere length of peripheral blood mononuclear cells in HIV-infected patients with advanced immunodeficiency. This telomere reduction concerns T4, T8, and B lymphocytes, providing evidence of high turnover of these cells in the course of HIV infection. These data suggest that replicative senescence could be involved in the final immunosuppression and may have important therapeutical implications.
Molecular and Cellular Biology, 2002
We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To ... more We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To this end, we established telomerase-positive cell lines in which the targeting of these telomeric proteins to specific telomeres could be induced. We demonstrate that their targeting leads to telomere shortening. This indicates that these proteins act in cis to repress telomere elongation. Inhibition of telomerase activity by a modified oligonucleotide did not further increase the pace of telomere erosion caused by TRF1 targeting, suggesting that telomerase itself is the target of TRF1 regulation. In contrast, TRF2 targeting and telomerase inhibition have additive effects. The possibility that TRF2 can activate a telomeric degradation pathway was directly tested in human primary cells that do not express telomerase. In these cells, overexpression of full-length TRF2 leads to an increased rate of telomere shortening.
Oncogene, 1999
Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been ... more Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been generally assumed that activation of telomerase prevents further telomere shortening and is essential for cell immortalization. In this study, we performed a detailed cytogenetic and molecular characterization of four SV40 transformed human ®broblastic cell lines by regularly monitoring the size distribution of terminal restriction fragments, telomerase activity and the associated chromosomal instability throughout immortalization. The mean TRF lengths progressively decreased in pre-crisis cells during the lifespan of the cultures. At crisis, telomeres reached a critical size, dierent among the cell lines, contributing to the peak of dicentric chromosomes, which resulted mostly from telomeric associations. We observed a direct correlation between short telomere length at crisis and chromosomal instability. In two immortal cell lines, although telomerase was detected, mean telomere length still continued to decrease whereas the number of dicentric chromosomes associated was stabilized. Thus telomerase could protect speci®cally telomeres which have reached a critical size against end-to-end dicentrics, while long telomeres continue to decrease, although at a slower rate as before crisis. This suggests a balance between elongation by telomerase and telomere shortening, towards a stabilized`optimal' length.
Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis, 1997
We have shown previously that radiation may induce a type of genetic instab ility in some cells t... more We have shown previously that radiation may induce a type of genetic instab ility in some cells that results in a persistent increase in the rate at which spontaneous mutations arise in their progeny over many generations of cell replicat ion. The present investigation was designed to determine : 1) the frequency of the hypermutable phenotype among clones derived from single cells surviving radiation exposure; 2) the dose response relationship for this effect; 3) its dependence on radiation quality; 4) the molecular structure of late-arising mutations; and 5) the relationslup between the delayed mutagenic effects of radiation and chromosomal instability.
arXiv (Cornell University), Dec 20, 2017
In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and ... more In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and biomedical research. Unfortunately, chromosomes often overlap and it is necessary to identify and distinguish between the overlapping chromosomes. A segmentation solution that is fast and automated will enable scaling of cost effective medicine and biomedical research. We apply neural network-based image segmentation to the problem of distinguishing between partially overlapping DNA chromosomes. A convolutional neural network is customized for this problem. The results achieved intersection over union (IOU) scores of 94.7% for the overlapping region and 88-94% on the non-overlapping chromosome regions.
Molecular and Cellular Biology, May 1, 2002
We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To ... more We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To this end, we established telomerase-positive cell lines in which the targeting of these telomeric proteins to specific telomeres could be induced. We demonstrate that their targeting leads to telomere shortening. This indicates that these proteins act in cis to repress telomere elongation. Inhibition of telomerase activity by a modified oligonucleotide did not further increase the pace of telomere erosion caused by TRF1 targeting, suggesting that telomerase itself is the target of TRF1 regulation. In contrast, TRF2 targeting and telomerase inhibition have additive effects. The possibility that TRF2 can activate a telomeric degradation pathway was directly tested in human primary cells that do not express telomerase. In these cells, overexpression of full-length TRF2 leads to an increased rate of telomere shortening.
Biochimie, 1995
The very end of the chromosome is called the telomere and is composed of DNA repeat sequences and... more The very end of the chromosome is called the telomere and is composed of DNA repeat sequences and associated proteins. Genetic and biochemical analyses of this complex, the telosome, lead to the hypothesis that transcription and DnA replication are submitted to position effects mediated by the telomere proximity. Telomere lengthr reduction and alterations of the telomeric chromatin assembly might explain the chromosome instability which occurs during the senescence and the immortalization process in vitro. A particular polymerase, the telomerase, is able to lengthen the telomeres. A telomerase activity was characterized in yeast, Tetrahymena, but also in transformed and in germline cells. We reviewed the involvement of telomeres in the aging process. We proposed that the short size of the telomere repeat at each chromosome could direct the loss of heterozygosity, t hus telomere length could play a role in individual and tissular susceptibility to develop cancer. Antitelomerase strategy for cancer therapy is attractive but limited by the short decrease of the telomere lenght at each cell division.
Biology of the Cell, Sep 1, 1999
Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been ... more Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been generally assumed that activation of telomerase prevents further telomere shortening and is essential for cell immortalization. In this study, we performed a detailed cytogenetic ...
ArXiv, 2017
In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and ... more In medicine, visualizing chromosomes is important for medical diagnostics, drug development, and biomedical research. Unfortunately, chromosomes often overlap and it is necessary to identify and distinguish between the overlapping chromosomes. A segmentation solution that is fast and automated will enable scaling of cost effective medicine and biomedical research. We apply neural network-based image segmentation to the problem of distinguishing between partially overlapping DNA chromosomes. A convolutional neural network is customized for this problem. The results achieved intersection over union (IOU) scores of 94.7% for the overlapping region and 88-94% on the non-overlapping chromosome regions.
Les telomeres sont des complexes nucleoproteiques localises a l'extremite des chromosomes euc... more Les telomeres sont des complexes nucleoproteiques localises a l'extremite des chromosomes eucaryotes. Les telomeres protegent les chromosomes d'une perte d'informations genetiques. Les motifs telomeriques (ttaggg)n etre restaures apres elongation par la telomerase. L'activite telomerase est faible ou absente dans les cellules somatiques cyclantes qui possedent un potentiel de division limite, tandis que les cellules immortelles, comme les cellules de la lignee germinale ou les cellules tumorales ont une activite elevee. Nous avons ameliores et concu de nouvelles techniques pour analyser la longueur des telomeres par southern-blot et par hybridation in-situ. La distribution de la longueur des telomeres a ete analysee dans des fibroblastes primaires jusqu'a la senescence, dans ces memes fibroblastes apres transformation par sv40 et dans des lymphocytes de patients vih +. Chez les patients vih+ avec moins de 200 t4 par mm3, on detecte une diminution de la longueur d...
Methods in molecular biology (Clifton, N.J.), 2002
ABSTRACT
Virology, 1997
Telomeres are complex protein-DNA structures located at the ends of eukaryotic chromosomes. In a ... more Telomeres are complex protein-DNA structures located at the ends of eukaryotic chromosomes. In a normal cell, telomere DNA shortens with cell divisions. Such a telomere loss may act as a mitotic clock to eventually signal cell cycling exit and cellular senescence. In a transversal study, we found a marked decrease in telomere length of peripheral blood mononuclear cells in HIV-infected patients with advanced immunodeficiency. This telomere reduction concerns T4, T8, and B lymphocytes, providing evidence of high turnover of these cells in the course of HIV infection. These data suggest that replicative senescence could be involved in the final immunosuppression and may have important therapeutical implications. ᭧ 1997 Academic Press these mechanisms remain poorly known, although an-148
Biology of the Cell, 1999
Biology of The Cell, 1999
Virology, 1997
Telomeres are complex protein–DNA structures located at the ends of eukaryotic chromosomes. In a ... more Telomeres are complex protein–DNA structures located at the ends of eukaryotic chromosomes. In a normal cell, telomere DNA shortens with cell divisions. Such a telomere loss may act as a mitotic clock to eventually signal cell cycling exit and cellular senescence. In a transversal study, we found a marked decrease in telomere length of peripheral blood mononuclear cells in HIV-infected patients with advanced immunodeficiency. This telomere reduction concerns T4, T8, and B lymphocytes, providing evidence of high turnover of these cells in the course of HIV infection. These data suggest that replicative senescence could be involved in the final immunosuppression and may have important therapeutical implications.
Molecular and Cellular Biology, 2002
We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To ... more We investigated the control of telomere length by the human telomeric proteins TRF1 and TRF2. To this end, we established telomerase-positive cell lines in which the targeting of these telomeric proteins to specific telomeres could be induced. We demonstrate that their targeting leads to telomere shortening. This indicates that these proteins act in cis to repress telomere elongation. Inhibition of telomerase activity by a modified oligonucleotide did not further increase the pace of telomere erosion caused by TRF1 targeting, suggesting that telomerase itself is the target of TRF1 regulation. In contrast, TRF2 targeting and telomerase inhibition have additive effects. The possibility that TRF2 can activate a telomeric degradation pathway was directly tested in human primary cells that do not express telomerase. In these cells, overexpression of full-length TRF2 leads to an increased rate of telomere shortening.
Oncogene, 1999
Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been ... more Loss of telomeric repeats during cell proliferation could play a role in senescence. It has been generally assumed that activation of telomerase prevents further telomere shortening and is essential for cell immortalization. In this study, we performed a detailed cytogenetic and molecular characterization of four SV40 transformed human ®broblastic cell lines by regularly monitoring the size distribution of terminal restriction fragments, telomerase activity and the associated chromosomal instability throughout immortalization. The mean TRF lengths progressively decreased in pre-crisis cells during the lifespan of the cultures. At crisis, telomeres reached a critical size, dierent among the cell lines, contributing to the peak of dicentric chromosomes, which resulted mostly from telomeric associations. We observed a direct correlation between short telomere length at crisis and chromosomal instability. In two immortal cell lines, although telomerase was detected, mean telomere length still continued to decrease whereas the number of dicentric chromosomes associated was stabilized. Thus telomerase could protect speci®cally telomeres which have reached a critical size against end-to-end dicentrics, while long telomeres continue to decrease, although at a slower rate as before crisis. This suggests a balance between elongation by telomerase and telomere shortening, towards a stabilized`optimal' length.
Mutation Research-fundamental and Molecular Mechanisms of Mutagenesis, 1997
We have shown previously that radiation may induce a type of genetic instab ility in some cells t... more We have shown previously that radiation may induce a type of genetic instab ility in some cells that results in a persistent increase in the rate at which spontaneous mutations arise in their progeny over many generations of cell replicat ion. The present investigation was designed to determine : 1) the frequency of the hypermutable phenotype among clones derived from single cells surviving radiation exposure; 2) the dose response relationship for this effect; 3) its dependence on radiation quality; 4) the molecular structure of late-arising mutations; and 5) the relationslup between the delayed mutagenic effects of radiation and chromosomal instability.