Zeina Al Natour - Academia.edu (original) (raw)
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Papers by Zeina Al Natour
![Research paper thumbnail of The Effects of Histone H1 and Benzo[a] Pyrene on Chromatin Modifying Complexes](https://attachments.academia-assets.com/99440723/thumbnails/1.jpg)
](Packaging of DNA into the condensed structure of chromatin presents a barrier to many cellular pr... more Packaging of DNA into the condensed structure of chromatin presents a barrier to many cellular processe that require DNA access such as transcription and replication. This problem is solved, in part, by the action of various complexes that modify the chromatin structure so that it becomes more accessible and, therefore, a more suitable platform for these processes. A TP-dependent chromatin remodeling complexes and histone acetyltransferases are examples of many chromatin modifying complexes that work to alleviate chromatin-mediated repression. Histone H I is an important component of chromatin which serves in both stabilizing and folding of chromatin into a higher order tructure. Many studies have demonstrated the importance of histone HI in gene regulation. Furthermore, histone H l has been suggested to affect the functions of modifying proteins. [n this study, we have used pull-down assay to test the effects of histone HI on the binding of two chromatin modifying complexes ( SWIfS...
Real-life problems are tending to become more complex as a result of expanding population, high l... more Real-life problems are tending to become more complex as a result of expanding population, high level of demand at all levels and the advancement of technology which became integrated into almost all aspects of life. Such complex problems can only be tackled by employing tools in multiples disciplines. The combination of disciplines in such research studies is dictated by the nature of the problem. Here we present our experience as a case study in which we conducted our research following an interdisciplinary research approach involving two disciplines of electrical engineering and biochemistry. We discuss the uniqueness of joint venture between the two disciplines, the obstacles faced and how they are tackled in addition to giving some recommendations that we believe can act as guidelines to scientists who are considering those two disciplines in their future research. Our observations and recommendations go in line with other findings, but we additionally provide real cases and ex...
Many studies have identified conserved ATP-dependent chromatin remodeling complexes whose functio... more Many studies have identified conserved ATP-dependent chromatin remodeling complexes whose functions are to modulate DNA access by relieving chromatinmediated repression. We have previously characterized Fun30 in Saccharomyces cerevisiae as a homodimer with ATP-dependent chromatin remodeling activity. Other studies have shown that Fun30 plays a role in maintaining the silenced state of subtelomeric and centromeric chromosomal regions. Fun30 has also been shown to play an important role in DNA damage repair by facilitating long range resection of DNA in Double Strand Breaks. This thesis was focuses on understanding the mechanisms by which Fun30 is involved in DNA damage repair. Results presented here show that Fun30 can anneal complementary strands of DNA that is facilitated by ATP hydrolysis and a helicase activity in the presence of trap DNA. In addition, Fun30 was found to be able to relax both negatively and positively supercoiled DNA in an ATP-independent manner and cleave a 3’ o...
DNA and cell biology, 2007
The linker histones are involved in the salt-dependent folding of the nucleosomes into higher-ord... more The linker histones are involved in the salt-dependent folding of the nucleosomes into higher-order chromatin structures. To better understand the mechanism of action of these histones in chromatin, we studied the interactions of the linker histone H1 with DNA at various histone/DNA ratios and at different ionic strengths. In direct competition experiments, we have confirmed the binding of H1 to superhelical DNA in preference to linear or nicked circular DNA forms. We show that the electrophoretic mobility of the H1/supercoiled DNA complex decreases with increasing H1 concentrations and increases with ionic strengths. These results indicate that the interaction of the linker histone H1 with supercoiled DNA results in a soluble binding of H1 with DNA at low H1 or salt concentrations and aggregation at higher H1 concentrations. Moreover, we show that H1 dissociates from the DNA or nucleosomes at high salt concentrations. By the immobilized template pull-down assay, we confirm these da...
Heliyon
Available methods for detecting blood in the urine (hematuria) can be problematic since results c... more Available methods for detecting blood in the urine (hematuria) can be problematic since results can be influenced by many factors in patients and in the lab settings, resulting in false positive or false negative results. This necessitates the development of new, accurate and easy-access methods that save time and effort. This study demonstrates a label-free and accurate method for detecting the presence of red and white blood cells (RBCs and WBCs) in urine by measuring the changes in the dielectric properties of urine upon increasing concentrations of both cell types. The current method could detect changes in the electrical properties of fresh urine over a short time interval, making this method suitable for detecting changes that cannot be recognized by conventional methods. Correcting for these changes enabled the detection of a minimum cell concentration of 10 2 RBCs per ml which is not possible by conventional methods used in the labs except for the semi-quantitative method that can detect 50 RBCs per ml, but it is a lengthy and involved procedure, not suitable for high volume labs. This ability to detect very small amount of both types of cells makes the proposed technique an attractive tool for detecting hematuria, the presence of which is indicative of problems in the excretory system.
IEEE Access
In this paper, we characterize and discriminate between normal and cancer cells from three differ... more In this paper, we characterize and discriminate between normal and cancer cells from three different tissue types, liver, lung, and breast, using capacitance-voltage-based extracted set of parameters. Cells from each type of cancer cell line were suspended in a liquid media either individually or as mixtures with their normal counterparts. Empirically, normal cells were observed to exhibit higher dielectric constants when compared to cancer cells from the same tissue. Moreover, adding cancer cells to normal cells was observed to increase the capacitance of normal cells, and the extent of this increase varied with the type of tissue tested with the lung cells causing the greatest change. This shows that the cancer cells of different cell origin possess their own signature electrical parameters, especially when compared with their normal counterparts, and that cancer cell seems to affect normal cells in a different manner, depending upon the tissue type. It was also noticed that the cells (both cancer and normal) exhibited a higher dielectric value as per the following order (from least to most): breast, lung, and liver. The changes in electrical parameters from normal to cancer state were explained not only by the modification of its physiological and biochemical properties but also by the morphological changes. This approach paves the way for exploring unique electrical signatures of normal and their corresponding cancer cells to enable their detection and discrimination. INDEX TERMS Capacitance-voltage measurements, cancer cells, electrical detection, dielectric constant, dielectric properties, normal cells, polarization.
IEEE Access
Finding non-invasive and label-free techniques that allow real-time monitoring of living cells is... more Finding non-invasive and label-free techniques that allow real-time monitoring of living cells is a field of intensive research with first trials dating back to a century. Employing dielectric spectroscopy on biological materials has aided in deciphering many aspects of living cells, such as cell structure and physiology. In this paper, we studied the dielectric parameters of budding yeast cell suspension as they progressed through the cell cycle. This was done by measuring the capacitance-voltage profile as well as other electrical parameters of cells at different phases of the cell cycle. For this purpose, cells were initially synchronized at the G1 phase and then released in the culture media. Samples at different time points were taken, and both electrical and flow cytometry analyses were carried out. In this paper, we have measured the electrical parameters of the yeast cells as they progress through the cell cycle at very low frequencies, which is believed to preserve all the mechanisms of polarization in yeast cell suspensions. In addition, this allows us to observe electrical changes independent of initial cell numbers. The results reveal an incremental increase in the capacitance-voltage profile as cells progressed through the cell cycle. The capacitance-voltage profile could be used to determine the doubling time of the yeast cells. Studying the yeast doubling time is important in the real-time assessment of different strains/mutants in terms of their progress through the cell cycle and any potential differences between yeast strains. Electrical-based techniques are more sensitive to small changes that occur in cells, which cannot be traced by other methods such as fluorescence-activated cell sorting (FACS). Moreover, if such a technique, used in this paper, is integrated into a multiplexing system, which allows parallel and simultaneous runs, it could potentially be more powerful than FACS for offering real-time automated measurements of cell cycle progress, avoiding the lengthy processing time required by FACS.
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, Jan 11, 2018
Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-n... more Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-negative breast cancers have the worst prognosis. The identification of new genes associated with triple-negative breast cancer progression is crucial for developing more specific anti-cancer targeted therapies, which could lead to a better management of these patients. In this context, we have recently demonstrated that SMARCAD1, a DEAD/H box-containing helicase, is involved in breast cancer cell migration, invasion, and metastasis. The aim of this study was to investigate the impact of the stable knockdown of SMARCAD1 on human breast cancer cell progression. Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of the stable knockdown of SMARCAD1 on human breast cancer cell proliferation and colony growth in vitro and on tumour growth in chick embryo and nude mouse xenograft models in vivo using MDA-MB-231 (ER-/PR-/ HER2-) and T47D (ER+/PR+/-/HER2-) human b...
DNA Repair, 2017
Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomole... more Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomolecules including DNA and consequently activates various DNA repair pathways. The nature of DNA damage and the cell cycle stage at which DNA damage occurs determine the appropriate repair pathway to rectify the damage. Oxidized DNA bases are primarily repaired by base excision repair and nucleotide incision repair. Nucleotide excision repair acts on lesions that distort DNA helix, mismatch repair on mispaired bases, and homologous recombination and non-homologous end joining on double stranded breaks. Post-replication repair that overcomes replication blocks caused by DNA damage also plays a crucial role in protecting the cell from the deleterious effects of oxidative DNA damage. Mitochondrial DNA is also prone to oxidative damage and is efficiently repaired by the cellular DNA repair machinery. In this review, we discuss the DNA repair pathways in relation to the nature of oxidative DNA damage in Saccharomyces cerevisiae.
Packaging of DNA into the condensed structure of chromatin presents a barrier to many cellular pr... more Packaging of DNA into the condensed structure of chromatin presents a barrier to many cellular processe that require DNA access such as transcription and replication. This problem is solved, in part, by the action of various complexes that modify the chromatin structure so that it becomes more accessible and, therefore, a more suitable platform for these processes. A TP-dependent chromatin remodeling complexes and histone acetyltransferases are examples of many chromatin modifying complexes that work to alleviate chromatin-mediated repression. Histone H I is an important component of chromatin which serves in both stabilizing and folding of chromatin into a higher order tructure. Many studies have demonstrated the importance of histone HI in gene regulation. Furthermore, histone H l has been suggested to affect the functions of modifying proteins. [n this study, we have used pull-down assay to test the effects of histone HI on the binding of two chromatin modifying complexes ( SWIfS...
Real-life problems are tending to become more complex as a result of expanding population, high l... more Real-life problems are tending to become more complex as a result of expanding population, high level of demand at all levels and the advancement of technology which became integrated into almost all aspects of life. Such complex problems can only be tackled by employing tools in multiples disciplines. The combination of disciplines in such research studies is dictated by the nature of the problem. Here we present our experience as a case study in which we conducted our research following an interdisciplinary research approach involving two disciplines of electrical engineering and biochemistry. We discuss the uniqueness of joint venture between the two disciplines, the obstacles faced and how they are tackled in addition to giving some recommendations that we believe can act as guidelines to scientists who are considering those two disciplines in their future research. Our observations and recommendations go in line with other findings, but we additionally provide real cases and ex...
Many studies have identified conserved ATP-dependent chromatin remodeling complexes whose functio... more Many studies have identified conserved ATP-dependent chromatin remodeling complexes whose functions are to modulate DNA access by relieving chromatinmediated repression. We have previously characterized Fun30 in Saccharomyces cerevisiae as a homodimer with ATP-dependent chromatin remodeling activity. Other studies have shown that Fun30 plays a role in maintaining the silenced state of subtelomeric and centromeric chromosomal regions. Fun30 has also been shown to play an important role in DNA damage repair by facilitating long range resection of DNA in Double Strand Breaks. This thesis was focuses on understanding the mechanisms by which Fun30 is involved in DNA damage repair. Results presented here show that Fun30 can anneal complementary strands of DNA that is facilitated by ATP hydrolysis and a helicase activity in the presence of trap DNA. In addition, Fun30 was found to be able to relax both negatively and positively supercoiled DNA in an ATP-independent manner and cleave a 3’ o...
DNA and cell biology, 2007
The linker histones are involved in the salt-dependent folding of the nucleosomes into higher-ord... more The linker histones are involved in the salt-dependent folding of the nucleosomes into higher-order chromatin structures. To better understand the mechanism of action of these histones in chromatin, we studied the interactions of the linker histone H1 with DNA at various histone/DNA ratios and at different ionic strengths. In direct competition experiments, we have confirmed the binding of H1 to superhelical DNA in preference to linear or nicked circular DNA forms. We show that the electrophoretic mobility of the H1/supercoiled DNA complex decreases with increasing H1 concentrations and increases with ionic strengths. These results indicate that the interaction of the linker histone H1 with supercoiled DNA results in a soluble binding of H1 with DNA at low H1 or salt concentrations and aggregation at higher H1 concentrations. Moreover, we show that H1 dissociates from the DNA or nucleosomes at high salt concentrations. By the immobilized template pull-down assay, we confirm these da...
Heliyon
Available methods for detecting blood in the urine (hematuria) can be problematic since results c... more Available methods for detecting blood in the urine (hematuria) can be problematic since results can be influenced by many factors in patients and in the lab settings, resulting in false positive or false negative results. This necessitates the development of new, accurate and easy-access methods that save time and effort. This study demonstrates a label-free and accurate method for detecting the presence of red and white blood cells (RBCs and WBCs) in urine by measuring the changes in the dielectric properties of urine upon increasing concentrations of both cell types. The current method could detect changes in the electrical properties of fresh urine over a short time interval, making this method suitable for detecting changes that cannot be recognized by conventional methods. Correcting for these changes enabled the detection of a minimum cell concentration of 10 2 RBCs per ml which is not possible by conventional methods used in the labs except for the semi-quantitative method that can detect 50 RBCs per ml, but it is a lengthy and involved procedure, not suitable for high volume labs. This ability to detect very small amount of both types of cells makes the proposed technique an attractive tool for detecting hematuria, the presence of which is indicative of problems in the excretory system.
IEEE Access
In this paper, we characterize and discriminate between normal and cancer cells from three differ... more In this paper, we characterize and discriminate between normal and cancer cells from three different tissue types, liver, lung, and breast, using capacitance-voltage-based extracted set of parameters. Cells from each type of cancer cell line were suspended in a liquid media either individually or as mixtures with their normal counterparts. Empirically, normal cells were observed to exhibit higher dielectric constants when compared to cancer cells from the same tissue. Moreover, adding cancer cells to normal cells was observed to increase the capacitance of normal cells, and the extent of this increase varied with the type of tissue tested with the lung cells causing the greatest change. This shows that the cancer cells of different cell origin possess their own signature electrical parameters, especially when compared with their normal counterparts, and that cancer cell seems to affect normal cells in a different manner, depending upon the tissue type. It was also noticed that the cells (both cancer and normal) exhibited a higher dielectric value as per the following order (from least to most): breast, lung, and liver. The changes in electrical parameters from normal to cancer state were explained not only by the modification of its physiological and biochemical properties but also by the morphological changes. This approach paves the way for exploring unique electrical signatures of normal and their corresponding cancer cells to enable their detection and discrimination. INDEX TERMS Capacitance-voltage measurements, cancer cells, electrical detection, dielectric constant, dielectric properties, normal cells, polarization.
IEEE Access
Finding non-invasive and label-free techniques that allow real-time monitoring of living cells is... more Finding non-invasive and label-free techniques that allow real-time monitoring of living cells is a field of intensive research with first trials dating back to a century. Employing dielectric spectroscopy on biological materials has aided in deciphering many aspects of living cells, such as cell structure and physiology. In this paper, we studied the dielectric parameters of budding yeast cell suspension as they progressed through the cell cycle. This was done by measuring the capacitance-voltage profile as well as other electrical parameters of cells at different phases of the cell cycle. For this purpose, cells were initially synchronized at the G1 phase and then released in the culture media. Samples at different time points were taken, and both electrical and flow cytometry analyses were carried out. In this paper, we have measured the electrical parameters of the yeast cells as they progress through the cell cycle at very low frequencies, which is believed to preserve all the mechanisms of polarization in yeast cell suspensions. In addition, this allows us to observe electrical changes independent of initial cell numbers. The results reveal an incremental increase in the capacitance-voltage profile as cells progressed through the cell cycle. The capacitance-voltage profile could be used to determine the doubling time of the yeast cells. Studying the yeast doubling time is important in the real-time assessment of different strains/mutants in terms of their progress through the cell cycle and any potential differences between yeast strains. Electrical-based techniques are more sensitive to small changes that occur in cells, which cannot be traced by other methods such as fluorescence-activated cell sorting (FACS). Moreover, if such a technique, used in this paper, is integrated into a multiplexing system, which allows parallel and simultaneous runs, it could potentially be more powerful than FACS for offering real-time automated measurements of cell cycle progress, avoiding the lengthy processing time required by FACS.
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, Jan 11, 2018
Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-n... more Breast cancer is the most common cancer in women worldwide, and within this cancer type, triple-negative breast cancers have the worst prognosis. The identification of new genes associated with triple-negative breast cancer progression is crucial for developing more specific anti-cancer targeted therapies, which could lead to a better management of these patients. In this context, we have recently demonstrated that SMARCAD1, a DEAD/H box-containing helicase, is involved in breast cancer cell migration, invasion, and metastasis. The aim of this study was to investigate the impact of the stable knockdown of SMARCAD1 on human breast cancer cell progression. Using two different designs of shRNA targeting SMARCAD1, we investigated the impact of the stable knockdown of SMARCAD1 on human breast cancer cell proliferation and colony growth in vitro and on tumour growth in chick embryo and nude mouse xenograft models in vivo using MDA-MB-231 (ER-/PR-/ HER2-) and T47D (ER+/PR+/-/HER2-) human b...
DNA Repair, 2017
Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomole... more Malfunction of enzymes that detoxify reactive oxygen species leads to oxidative attack on biomolecules including DNA and consequently activates various DNA repair pathways. The nature of DNA damage and the cell cycle stage at which DNA damage occurs determine the appropriate repair pathway to rectify the damage. Oxidized DNA bases are primarily repaired by base excision repair and nucleotide incision repair. Nucleotide excision repair acts on lesions that distort DNA helix, mismatch repair on mispaired bases, and homologous recombination and non-homologous end joining on double stranded breaks. Post-replication repair that overcomes replication blocks caused by DNA damage also plays a crucial role in protecting the cell from the deleterious effects of oxidative DNA damage. Mitochondrial DNA is also prone to oxidative damage and is efficiently repaired by the cellular DNA repair machinery. In this review, we discuss the DNA repair pathways in relation to the nature of oxidative DNA damage in Saccharomyces cerevisiae.