Search

Your search keyword '"Pounami Samadder"' showing total 6 results
Start Over Author "Pounami Samadder"
6 results on '"Pounami Samadder"'

1. MUS81 cleaves TOP1-derived lesions and other DNA–protein cross-links

Author

Victoria Marini, Fedor Nikulenkov, Pounami Samadder, Sissel Juul, Birgitta R. Knudsen, and Lumir Krejci

Subjects
DNA-protein cross-links repair, MUS81, TDP1, Topoisomerase 1, Biology (General), QH301-705.5
Abstract

Abstract Background DNA-protein cross-links (DPCs) are one of the most deleterious DNA lesions, originating from various sources, including enzymatic activity. For instance, topoisomerases, which play a fundamental role in DNA metabolic processes such as replication and transcription, can be trapped and remain covalently bound to DNA in the presence of poisons or nearby DNA damage. Given the complexity of individual DPCs, numerous repair pathways have been described. The protein tyrosyl-DNA phosphodiesterase 1 (Tdp1) has been demonstrated to be responsible for removing topoisomerase 1 (Top1). Nevertheless, studies in budding yeast have indicated that alternative pathways involving Mus81, a structure-specific DNA endonuclease, could also remove Top1 and other DPCs. Results This study shows that MUS81 can efficiently cleave various DNA substrates modified by fluorescein, streptavidin or proteolytically processed topoisomerase. Furthermore, the inability of MUS81 to cleave substrates bearing native TOP1 suggests that TOP1 must be either dislodged or partially degraded prior to MUS81 cleavage. We demonstrated that MUS81 could cleave a model DPC in nuclear extracts and that depletion of TDP1 in MUS81-KO cells induces sensitivity to the TOP1 poison camptothecin (CPT) and affects cell proliferation. This sensitivity is only partially suppressed by TOP1 depletion, indicating that other DPCs might require the MUS81 activity for cell proliferation. Conclusions Our data indicate that MUS81 and TDP1 play independent roles in the repair of CPT-induced lesions, thus representing new therapeutic targets for cancer cell sensitisation in combination with TOP1 inhibitors.

Published
2023
Full Text
View/download PDF

2. Supplementary file-Synthesis from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation

Author

Karel Souček, Kamil Paruch, Lumír Krejčí, Aleš Hampl, Josef Jaroš, Milan Ešner, Radek Fedr, Peter Kollár, Petra Ovesná, Miroslava Bittová, Lucia Binó, Hana Kolářová, Kateřina Vašíčková, Petr Vaňhara, Nicol Straková, Stanislav Drápela, Fedor Nikulenkov, Prashant Khirsariya, Ondřej Hylse, Tereza Suchánková, and Pounami Samadder

Abstract

Detail description of synthesis and supporting data

Published
2023

3. Supplementary Methods from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation

Author

Karel Souček, Kamil Paruch, Lumír Krejčí, Aleš Hampl, Josef Jaroš, Milan Ešner, Radek Fedr, Peter Kollár, Petra Ovesná, Miroslava Bittová, Lucia Binó, Hana Kolářová, Kateřina Vašíčková, Petr Vaňhara, Nicol Straková, Stanislav Drápela, Fedor Nikulenkov, Prashant Khirsariya, Ondřej Hylse, Tereza Suchánková, and Pounami Samadder

Abstract

Detail description of Material and Methods

Published
2023

4. Supplementary Figures from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation

Author

Karel Souček, Kamil Paruch, Lumír Krejčí, Aleš Hampl, Josef Jaroš, Milan Ešner, Radek Fedr, Peter Kollár, Petra Ovesná, Miroslava Bittová, Lucia Binó, Hana Kolářová, Kateřina Vašíčková, Petr Vaňhara, Nicol Straková, Stanislav Drápela, Fedor Nikulenkov, Prashant Khirsariya, Ondřej Hylse, Tereza Suchánková, and Pounami Samadder

Abstract

Figure S1. In vitro profiling of SCH900776 and its selected analogs. Figure S2. Analogs of MU380 with the N-trifluoromethylpyrazol pharmacophore. Figure S3. Dot plots of flow cytometric analysis using γH2AX and Annexin V staining related to Figure 2D. Figure S4. Dose response curves of relative viability of the tested cell lines treated with CHK1 inhibitors at indicated concentrations in combination with HU in the concentration range shown on the x-axis (related to Figure 3A). Figure S5. Dynamics of cytotoxic effects of CHK1 inhibitors alone and in combination with HU. Figure S6. Dose response curves of relative viability of the tested cell lines treated with CHK1 inhibitors at indicated concentration in combination with GEM in concentration range shown on the x-axis (related to Figure 3B). Figure S7. Dose response curves of relative viability of the tested cell lines treated with CHK1 inhibitors at indicated concentration in combination with irradiation in the dose range shown on the x-axis. Figure S8. Western blot analysis of total CHK1 and p-CHK1 (S296) levels in a panel of selected cell lines after indicated treatments. Figure S9. Drug retention analysis. Figure S10. MU380 induces CHK1 pS345 in mice hair follicles. Figure S11. Bioluminescent signal of SHO mice bearing MiaPaCa2 luc xenografts treated with GEM, SCH900776, or MU380 alone or in indicated combinations. Weight of MiaPaCa2 luc tumor-bearing animals. Representative images of γH2AX staining in MiaPaCa2 luc tumor sections.

Published
2023

5. Supplementary Legends from Synthesis and Profiling of a Novel Potent Selective Inhibitor of CHK1 Kinase Possessing Unusual N-trifluoromethylpyrazole Pharmacophore Resistant to Metabolic N-dealkylation

Author

Karel Souček, Kamil Paruch, Lumír Krejčí, Aleš Hampl, Josef Jaroš, Milan Ešner, Radek Fedr, Peter Kollár, Petra Ovesná, Miroslava Bittová, Lucia Binó, Hana Kolářová, Kateřina Vašíčková, Petr Vaňhara, Nicol Straková, Stanislav Drápela, Fedor Nikulenkov, Prashant Khirsariya, Ondřej Hylse, Tereza Suchánková, and Pounami Samadder

Abstract

Supplementary Legends for Supplemetary Figure S1 - S11

Published
2023

6. Cancer TARGETases: DSB repair as a pharmacological target

Author

Rakesh Aithal, Pounami Samadder, Lumir Krejci, and Ondrej Belan

Subjects
0301 basic medicine, Genome instability, DNA Repair, DNA damage, DNA repair, Bioinformatics, 03 medical and health sciences, XRCC1, Neoplasms, medicine, Animals, Humans, Pharmacology (medical), DNA Breaks, Double-Stranded, Molecular Targeted Therapy, Pharmacology, biology, Helicase, Cancer, medicine.disease, 3. Good health, Proliferating cell nuclear antigen, 030104 developmental biology, Cancer cell, biology.protein, Cancer research
Abstract

Cancer is a disease attributed to the accumulation of DNA damages due to incapacitation of DNA repair pathways resulting in genomic instability and a mutator phenotype. Among the DNA lesions, double stranded breaks (DSBs) are the most toxic forms of DNA damage which may arise as a result of extrinsic DNA damaging agents or intrinsic replication stress in fast proliferating cancer cells. Accurate repair of DSBs is therefore paramount to the cell survival, and several classes of proteins such as kinases, nucleases, helicases or core recombinational proteins have pre-defined jobs in precise execution of DSB repair pathways. On one hand, the proper functioning of these proteins ensures maintenance of genomic stability in normal cells, and on the other hand results in resistance to various drugs employed in cancer therapy and therefore presents a suitable opportunity for therapeutic targeting. Higher relapse and resistance in cancer patients due to non-specific, cytotoxic therapies is an alarming situation and it is becoming more evident to employ personalized treatment based on the genetic landscape of the cancer cells. For the success of personalized treatment, it is of immense importance to identify more suitable targetable proteins in DSB repair pathways and also to explore new synthetic lethal interactions with these pathways. Here we review the various alternative approaches to target the various protein classes termed as cancer TARGETases in DSB repair pathway to obtain more beneficial and selective therapy.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results