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1. Synthesis and biological evaluation of biaryl alkyl ethers as inhibitors of IDO1

Author

Markwalder, Jay A., primary, Balog, Aaron J., additional, Williams, David K., additional, Nara, Susheel J., additional, Reddy, Ratnakar, additional, Roy, Saumya, additional, Kanyaboina, Yadagiri, additional, Li, Xin, additional, Johnston, Kathy, additional, Fan, Yi, additional, Lewis, Hal, additional, Marsilio, Frank, additional, Yan, Chunhong, additional, Critton, David, additional, Newitt, John A., additional, Traeger, Sarah C., additional, Wu, Dauh-Rurng, additional, Jure-Kunkel, Maria N., additional, Jayaraman, Lata, additional, Lin, Tai-An, additional, Sinz, Michael W., additional, Hunt, John T., additional, and Seitz, Steven P., additional

Published
2023
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2. Supplementary Information Figure S5 from Dissecting Therapeutic Resistance to ERK Inhibition

Author

Jha, Sharda, primary, Morris, Erick J., primary, Hruza, Alan, primary, Mansueto, My Sam, primary, Schroeder, Gottfried K., primary, Arbanas, Jaren, primary, McMasters, Daniel, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Black, Stuart, primary, Elsen, Nathaniel L., primary, Mannarino, Anthony, primary, Cooper, Alan, primary, Fawell, Stephen, primary, Zawel, Leigh, primary, Jayaraman, Lata, primary, and Samatar, Ahmed A., primary

Published
2023
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3. Data from Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

Author

Morris, Erick J., primary, Jha, Sharda, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Zhu, Hugh, primary, Cooper, Alan, primary, Carr, Donna, primary, Deng, Yongi, primary, Jin, Weihong, primary, Black, Stuart, primary, Long, Brian, primary, Liu, Jenny, primary, DiNunzio, Edward, primary, Windsor, William, primary, Zhang, Rumin, primary, Zhao, Shuxia, primary, Angagaw, Minilik H., primary, Pinheiro, Elaine M., primary, Desai, Jagdish, primary, Xiao, Li, primary, Shipps, Gerald, primary, Hruza, Alan, primary, Wang, James, primary, Kelly, Joe, primary, Paliwal, Sunil, primary, Gao, Xiaolei, primary, Babu, Boga Sobhana, primary, Zhu, Liang, primary, Daublain, Pierre, primary, Zhang, Ling, primary, Lutterbach, Bart A., primary, Pelletier, Marc R., primary, Philippar, Ulrike, primary, Siliphaivanh, Phieng, primary, Witter, David, primary, Kirschmeier, Paul, primary, Bishop, W. Robert, primary, Hicklin, Daniel, primary, Gilliland, D. Gary, primary, Jayaraman, Lata, primary, Zawel, Leigh, primary, Fawell, Stephen, primary, and Samatar, Ahmed A., primary

Published
2023
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4. Supplementary Table S1 from Dissecting Therapeutic Resistance to ERK Inhibition

Author

Jha, Sharda, primary, Morris, Erick J., primary, Hruza, Alan, primary, Mansueto, My Sam, primary, Schroeder, Gottfried K., primary, Arbanas, Jaren, primary, McMasters, Daniel, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Black, Stuart, primary, Elsen, Nathaniel L., primary, Mannarino, Anthony, primary, Cooper, Alan, primary, Fawell, Stephen, primary, Zawel, Leigh, primary, Jayaraman, Lata, primary, and Samatar, Ahmed A., primary

Published
2023
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5. Supplementary Information text S1 from Dissecting Therapeutic Resistance to ERK Inhibition

Author

Jha, Sharda, primary, Morris, Erick J., primary, Hruza, Alan, primary, Mansueto, My Sam, primary, Schroeder, Gottfried K., primary, Arbanas, Jaren, primary, McMasters, Daniel, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Black, Stuart, primary, Elsen, Nathaniel L., primary, Mannarino, Anthony, primary, Cooper, Alan, primary, Fawell, Stephen, primary, Zawel, Leigh, primary, Jayaraman, Lata, primary, and Samatar, Ahmed A., primary

Published
2023
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6. Supplementary Figures from Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

Author

Morris, Erick J., primary, Jha, Sharda, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Zhu, Hugh, primary, Cooper, Alan, primary, Carr, Donna, primary, Deng, Yongi, primary, Jin, Weihong, primary, Black, Stuart, primary, Long, Brian, primary, Liu, Jenny, primary, DiNunzio, Edward, primary, Windsor, William, primary, Zhang, Rumin, primary, Zhao, Shuxia, primary, Angagaw, Minilik H., primary, Pinheiro, Elaine M., primary, Desai, Jagdish, primary, Xiao, Li, primary, Shipps, Gerald, primary, Hruza, Alan, primary, Wang, James, primary, Kelly, Joe, primary, Paliwal, Sunil, primary, Gao, Xiaolei, primary, Babu, Boga Sobhana, primary, Zhu, Liang, primary, Daublain, Pierre, primary, Zhang, Ling, primary, Lutterbach, Bart A., primary, Pelletier, Marc R., primary, Philippar, Ulrike, primary, Siliphaivanh, Phieng, primary, Witter, David, primary, Kirschmeier, Paul, primary, Bishop, W. Robert, primary, Hicklin, Daniel, primary, Gilliland, D. Gary, primary, Jayaraman, Lata, primary, Zawel, Leigh, primary, Fawell, Stephen, primary, and Samatar, Ahmed A., primary

Published
2023
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7. Data from Dissecting Therapeutic Resistance to ERK Inhibition

Author

Jha, Sharda, primary, Morris, Erick J., primary, Hruza, Alan, primary, Mansueto, My Sam, primary, Schroeder, Gottfried K., primary, Arbanas, Jaren, primary, McMasters, Daniel, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Black, Stuart, primary, Elsen, Nathaniel L., primary, Mannarino, Anthony, primary, Cooper, Alan, primary, Fawell, Stephen, primary, Zawel, Leigh, primary, Jayaraman, Lata, primary, and Samatar, Ahmed A., primary

Published
2023
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8. Supplementary Figure Legends from Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

Author

Morris, Erick J., primary, Jha, Sharda, primary, Restaino, Clifford R., primary, Dayananth, Priya, primary, Zhu, Hugh, primary, Cooper, Alan, primary, Carr, Donna, primary, Deng, Yongi, primary, Jin, Weihong, primary, Black, Stuart, primary, Long, Brian, primary, Liu, Jenny, primary, DiNunzio, Edward, primary, Windsor, William, primary, Zhang, Rumin, primary, Zhao, Shuxia, primary, Angagaw, Minilik H., primary, Pinheiro, Elaine M., primary, Desai, Jagdish, primary, Xiao, Li, primary, Shipps, Gerald, primary, Hruza, Alan, primary, Wang, James, primary, Kelly, Joe, primary, Paliwal, Sunil, primary, Gao, Xiaolei, primary, Babu, Boga Sobhana, primary, Zhu, Liang, primary, Daublain, Pierre, primary, Zhang, Ling, primary, Lutterbach, Bart A., primary, Pelletier, Marc R., primary, Philippar, Ulrike, primary, Siliphaivanh, Phieng, primary, Witter, David, primary, Kirschmeier, Paul, primary, Bishop, W. Robert, primary, Hicklin, Daniel, primary, Gilliland, D. Gary, primary, Jayaraman, Lata, primary, Zawel, Leigh, primary, Fawell, Stephen, primary, and Samatar, Ahmed A., primary

Published
2023
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9. Data from Preclinical Efficacy of Bevacizumab with CRLX101, an Investigational Nanoparticle–Drug Conjugate, in Treatment of Metastatic Triple-Negative Breast Cancer

Author

Pham, Elizabeth, primary, Yin, Melissa, primary, Peters, Christian G., primary, Lee, Christina R., primary, Brown, Donna, primary, Xu, Ping, primary, Man, Shan, primary, Jayaraman, Lata, primary, Rohde, Ellen, primary, Chow, Annabelle, primary, Lazarus, Douglas, primary, Eliasof, Scott, primary, Foster, F. Stuart, primary, and Kerbel, Robert S., primary

Published
2023
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10. Supplemental Figures S1-S6 from Preclinical Efficacy of Bevacizumab with CRLX101, an Investigational Nanoparticle–Drug Conjugate, in Treatment of Metastatic Triple-Negative Breast Cancer

Author

Pham, Elizabeth, primary, Yin, Melissa, primary, Peters, Christian G., primary, Lee, Christina R., primary, Brown, Donna, primary, Xu, Ping, primary, Man, Shan, primary, Jayaraman, Lata, primary, Rohde, Ellen, primary, Chow, Annabelle, primary, Lazarus, Douglas, primary, Eliasof, Scott, primary, Foster, F. Stuart, primary, and Kerbel, Robert S., primary

Published
2023
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11. Supplemental Methods from Preclinical Efficacy of Bevacizumab with CRLX101, an Investigational Nanoparticle–Drug Conjugate, in Treatment of Metastatic Triple-Negative Breast Cancer

Author

Pham, Elizabeth, primary, Yin, Melissa, primary, Peters, Christian G., primary, Lee, Christina R., primary, Brown, Donna, primary, Xu, Ping, primary, Man, Shan, primary, Jayaraman, Lata, primary, Rohde, Ellen, primary, Chow, Annabelle, primary, Lazarus, Douglas, primary, Eliasof, Scott, primary, Foster, F. Stuart, primary, and Kerbel, Robert S., primary

Published
2023
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12. Supplementary Figure S1 from CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α

Author

Tian, Xi, primary, Nguyen, Minh, primary, Foote, Henry P., primary, Caster, Joseph M., primary, Roche, Kyle C., primary, Peters, Christian G., primary, Wu, Pauline, primary, Jayaraman, Lata, primary, Garmey, Edward G., primary, Tepper, Joel E., primary, Eliasof, Scott, primary, and Wang, Andrew Z., primary

Published
2023
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13. Data from CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α

Author

Tian, Xi, primary, Nguyen, Minh, primary, Foote, Henry P., primary, Caster, Joseph M., primary, Roche, Kyle C., primary, Peters, Christian G., primary, Wu, Pauline, primary, Jayaraman, Lata, primary, Garmey, Edward G., primary, Tepper, Joel E., primary, Eliasof, Scott, primary, and Wang, Andrew Z., primary

Published
2023
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14. The discovery of BMS-737 as a potent, CYP17 lyase-selective inhibitor for the treatment of castration-resistant prostate cancer

Author

Padmakar Darne, Chetan, primary, Velaparthi, Upender, additional, Saulnier, Mark, additional, Frennesson, David, additional, Liu, Peiying, additional, Huang, Audris, additional, Tokarski, John, additional, Fura, Aberra, additional, Spires, Thomas, additional, Newitt, John, additional, Spires, Vanessa M., additional, Obermeier, Mary T., additional, Elzinga, Paul A., additional, Gottardis, Marco M., additional, Jayaraman, Lata, additional, Vite, Gregory D., additional, and Balog, Aaron, additional

Published
2022
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16. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-Beta signaling

Author

Shi, Yigong, Wang, Yan-Fei, Jayaraman, Lata, Yang, Haijuan, Massague, Joan, and Pavletich, Nikola P.

Subjects
Protein binding -- Research, DNA binding proteins -- Research, Transforming growth factors -- Research, Cytokines -- Research, Biological sciences
Abstract

A new DNA binding motif was revealed when the crystal structure of a Smad3 MH1 domain bound to a DNA sequence was examined using a 2.8 armstrong resolution X-ray. An 11-residue Beta hairpin embedded in the DNA provides the base-specific DNA recognition in the crystals. A surface loop region, where tumorigenic map, was found to be a functional surface that is important for Smad activity.

Published
1998

17. High mobility group protein-1 (HMG-1) is a unique activator of p53

Author

Jayaraman, Lata, Moorthy, Narayani Chandra, Murthy, Kanneganti G.K., Manley, James L., Bustin, Michael, and Prives, Carol

Subjects
DNA binding proteins -- Research, Genetic transcription -- Regulation, Biological sciences
Abstract

Binding of p53 protein to DNA is set off by interaction with covalent and noncovalent modifiers. Identification of a factor from HeLa nuclear extracts that start up p53 CNA binding has been achieved. It was found to be a high-mobility group protein, HMG-1, and belongs to a family of much-conserved chromatin-associated nucleoproteins. Members of the family bend DNA and aid binding of some transcription factors to cognate DNA sequences. Recombinant His-tagged HMG-1 helps in p53 DNA binding in vitro and HMG-1; p53 can interact directly in vitro. HMG-1 is unique as an activator of p53.

Published
1998

18. Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus

Author

Jayaraman, Lata and Prives, Carol

Subjects
Tumor suppressor genes -- Research, DNA binding proteins -- Analysis, Biological sciences
Abstract

Short single stranded DNA nucleotides having 16-40 nucleotides can stimulate the binding of human and murine p53 proteins to a p53 response element in supercoiled DNA but not the binding of a split p53 in which the C-terminal is missing. The p53 tumor suppressor protein which is activated when DNA is damaged, has an activation center, a DNA binding domain and an oligomerization domain. p53 activates many genes when the concentration of DNA damaging agents is high.

Published
1995

19. Activation of p53 sequence-specific DNA bindingby short single strands of DNA requires the p53 C-terminus

Author

Jayaraman, Lata and Prives, Carol

Subjects
Tumor proteins -- Analysis, Protein binding -- Analysis, DNA -- Analysis, Biological sciences
Abstract

Byline: Lata Jayaraman, Carol Prives Abstract: Upon cellular DNA damage, the p53 tumor suppressor protein transmits a signal to genes that control the cell cycle and apoptosis. One function of p53 that is important for its role in this pathway is its ability to function as a sequence-specific transcriptional activator. We demonstrate here that short single DNA strands can markedly stimulate the ability of human and murine p53 proteins to bind specifically to a p53 response element in supercoiled DNA. We also show that single-stranded DNA does not stimulate binding by a truncated p53 that lacks the C-terminal domain. Finally, we establish that a peptide spanning the p53 C-terminus has the ability in trans to stimulate sequence-specific DNA binding by p53 dramatically. These data taken together suggest a model in which the p53 C-terminus can recognize DNA structures resulting from damage-induced lesions, and this interaction can be propagated to regulate positively p53 sequence-specific DNA binding. Author Affiliation: Department of Biological SciencesColumbia University New York, New York 10027, USA

Published
1995

22. Stool donor qualification and collection from metastatic melanoma (MM) patients (pts) who have responded to checkpoint inhibitors (CPI) for manufacturing of fecal microbiota transplantation (FMT).

Author

Burton, Elizabeth M., primary, Glitza, Isabella Claudia, additional, Mahoney, Jennifer, additional, Wortman, Jennifer, additional, Aunis, John, additional, Litcofsky, Kevin, additional, Cook, David, additional, Jayaraman, Lata, additional, Ibrahim, Ramy A., additional, LaVallee, Theresa, additional, Tawbi, Hussein Abdul-Hassan, additional, and Wargo, Jennifer A., additional

Published
2019
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26. A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit

Author

Kopinja, Johnny, primary, Sevilla, Raquel S., additional, Levitan, Diane, additional, Dai, David, additional, Vanko, Amy, additional, Spooner, Edward, additional, Ware, Chris, additional, Forget, Robert, additional, Hu, Kun, additional, Kral, Astrid, additional, Spacciapoli, Peter, additional, Kennan, Richard, additional, Jayaraman, Lata, additional, Pucci, Vincenzo, additional, Perera, Samanthi, additional, Zhang, Weisheng, additional, Fischer, Christian, additional, and Lam, Michael H., additional

Published
2017
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27. Abstract 5135: Sustained and controlledin vivotherapeutic levels of drug payloads in tumors using two separate drug combination platforms: Antibody nanoparticle-drug conjugates and multi-drug nanoparticle-drug conjugates, with the potential for improved drug combinability and anticancer effects

Author

Metcalf, Chester A., primary, Poll, Derek van der, additional, Zhao, Liang, additional, Case, Roy I., additional, Lazarus, Doug, additional, Brown, Donna, additional, Halo, Tiffany, additional, Jayaraman, Lata, additional, Peters, Christian, additional, Rohde, Ellen, additional, and Eliasof, Scott, additional

Published
2017
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28. Abstract PR10: Significant improvements in therapeutic index for conjugated payloads using a nanoparticle-drug conjugate (NDC) platform to provide sustained drug release and potentially improved anticancer effects

Author

Metcalf, Chester, primary, Poll, Derek van der, additional, Zhao, Liang, additional, Halo, Tiffany, additional, Lazarus, Doug, additional, Stockmann, Adam, additional, Peters, Christian, additional, Brown, Donna, additional, Case, Roy, additional, Rohde, Ellen, additional, Jayaraman, Lata, additional, Wang, Hongwei, additional, Crowell, Tiffany, additional, Senderowicz, Adrian, additional, and Eliasof, Scott, additional

Published
2017
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29. CRLX101, a Nanoparticle–Drug Conjugate Containing Camptothecin, Improves Rectal Cancer Chemoradiotherapy by Inhibiting DNA Repair and HIF1α

Author

Tian, Xi, primary, Nguyen, Minh, additional, Foote, Henry P., additional, Caster, Joseph M., additional, Roche, Kyle C., additional, Peters, Christian G., additional, Wu, Pauline, additional, Jayaraman, Lata, additional, Garmey, Edward G., additional, Tepper, Joel E., additional, Eliasof, Scott, additional, and Wang, Andrew Z., additional

Published
2017
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30. Preclinical Efficacy of Bevacizumab with CRLX101, an Investigational Nanoparticle–Drug Conjugate, in Treatment of Metastatic Triple-Negative Breast Cancer

Author

Pham, Elizabeth, primary, Yin, Melissa, additional, Peters, Christian G., additional, Lee, Christina R., additional, Brown, Donna, additional, Xu, Ping, additional, Man, Shan, additional, Jayaraman, Lata, additional, Rohde, Ellen, additional, Chow, Annabelle, additional, Lazarus, Douglas, additional, Eliasof, Scott, additional, Foster, F. Stuart, additional, and Kerbel, Robert S., additional

Published
2016
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34. Dissecting Therapeutic Resistance to ERK Inhibition

Author

Jha, Sharda, primary, Morris, Erick J., additional, Hruza, Alan, additional, Mansueto, My Sam, additional, Schroeder, Gottfried K., additional, Arbanas, Jaren, additional, McMasters, Daniel, additional, Restaino, Clifford R., additional, Dayananth, Priya, additional, Black, Stuart, additional, Elsen, Nathaniel L., additional, Mannarino, Anthony, additional, Cooper, Alan, additional, Fawell, Stephen, additional, Zawel, Leigh, additional, Jayaraman, Lata, additional, and Samatar, Ahmed A., additional

Published
2016
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35. Discovery of the Selective CYP17A1 Lyase Inhibitor BMS-351 for the Treatment of Prostate Cancer

Author

Huang, Audris, primary, Jayaraman, Lata, additional, Fura, Aberra, additional, Vite, Gregory D., additional, Trainor, George L., additional, Gottardis, Marco M., additional, Spires, Thomas E., additional, Spires, Vanessa M., additional, Rizzo, Cheryl A., additional, Obermeier, Mary T., additional, Elzinga, Paul A., additional, Todderud, Gordon, additional, Fan, Yi, additional, Newitt, John A., additional, Beyer, Sophie M., additional, Zhu, Yongxin, additional, Warrack, Bethanne M., additional, Goodenough, Angela K., additional, Tebben, Andrew J., additional, Doweyko, Arthur M., additional, Gold, David L., additional, and Balog, Aaron, additional

Published
2015
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37. HIF inhibition in metastatic renal cell carcinoma (mRCC): Final results of a phase Ib /IIa clinical trial evaluating the nanoparticle drug conjugate (NDC), CRLX101, in combination with bevacizumab (bev).

Author

Keefe, Stephen Michael, primary, Hoffman-Censits, Jean H., additional, Mamtani, Ronac, additional, Walicki, Mary, additional, Robinson, Janelle, additional, Smith, Abigail, additional, Gunnarsson, Orvar, additional, Piscitelli, Anthony, additional, Hennessey, Meliessa, additional, Jayaraman, Lata, additional, Nixon, Andrew B., additional, Eliasof, Scott, additional, Cohen, Roger B., additional, Vaughn, David J., additional, Garmey, Edward Graeme, additional, and Haas, Naomi B., additional

Published
2015
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40. Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

Author

Morris, Erick J., primary, Jha, Sharda, additional, Restaino, Clifford R., additional, Dayananth, Priya, additional, Zhu, Hugh, additional, Cooper, Alan, additional, Carr, Donna, additional, Deng, Yongi, additional, Jin, Weihong, additional, Black, Stuart, additional, Long, Brian, additional, Liu, Jenny, additional, DiNunzio, Edward, additional, Windsor, William, additional, Zhang, Rumin, additional, Zhao, Shuxia, additional, Angagaw, Minilik H., additional, Pinheiro, Elaine M., additional, Desai, Jagdish, additional, Xiao, Li, additional, Shipps, Gerald, additional, Hruza, Alan, additional, Wang, James, additional, Kelly, Joe, additional, Paliwal, Sunil, additional, Gao, Xiaolei, additional, Babu, Boga Sobhana, additional, Zhu, Liang, additional, Daublain, Pierre, additional, Zhang, Ling, additional, Lutterbach, Bart A., additional, Pelletier, Marc R., additional, Philippar, Ulrike, additional, Siliphaivanh, Phieng, additional, Witter, David, additional, Kirschmeier, Paul, additional, Bishop, W. Robert, additional, Hicklin, Daniel, additional, Gilliland, D. Gary, additional, Jayaraman, Lata, additional, Zawel, Leigh, additional, Fawell, Stephen, additional, and Samatar, Ahmed A., additional

Published
2013
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43. Structural basis for CARM1 inhibition by indole and pyrazole inhibitors

Author

Sack, John S., primary, Thieffine, Sandrine, additional, Bandiera, Tiziano, additional, Fasolini, Marina, additional, Duke, Gerald J., additional, Jayaraman, Lata, additional, Kish, Kevin F., additional, Klei, Herbert E., additional, Purandare, Ashok V., additional, Rosettani, Pamela, additional, Troiani, Sonia, additional, Xie, Dianlin, additional, and Bertrand, Jay A., additional

Published
2011
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49. Crystal Structure of a Smad MH1 Domain Bound to DNA Insights on DNA Binding in TGF-β Signaling

Author

Shi, Yigong, Wang, Yan-Fei, Jayaraman, Lata, Yang, Haijuan, Massagué, Joan, and Pavletich, Nikola P.

Abstract

The Smad family of proteins, which are frequently targeted by tumorigenic mutations in cancer, mediate TGF-β signaling from cell membrane to nucleus. The crystal structure of a Smad3 MH1 domain bound to an optimal DNA sequence determined at 2.8 Å resolution reveals a novel DNA-binding motif. In the crystals, base-specific DNA recognition is provided exclusively by a conserved 11-residue β hairpin that is embedded in the major groove of DNA. A surface loop region, to which tumorigenic mutations map, has been identified as a functional surface important for Smad activity. This structure establishes a framework for understanding how Smad proteins may act in concert with other transcription factors in the regulation of TGF-β-responsive genes.

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50. Complex Formation between p53 and Replication Protein A Inhibits the Sequence-Specific DNA Binding of p53 and Is Regulated by Single-Stranded DNA

Author

Miller, Scott D., Moses, Kevin, Jayaraman, Lata, and Prives, Carol

Abstract

Human replication protein A (RP-A) (also known as human single-stranded DNA binding protein, or HSSB) is a multisubunit complex involved in both DNA replication and repair. Potentially important to both these functions, it is also capable of complex formation with the tumor suppressor protein p53. Here we show that although p53 is unable to prevent RP-A from associating with a range of single-stranded DNAs in solution, RP-A is able to strongly inhibit p53 from functioning as a sequence-specific DNA binding protein when the two proteins are complexed. This inhibition, in turn, can be regulated by the presence of various lengths of single-stranded DNAs, as RP-A, when bound to these single-stranded DNAs, is unable to interact with p53. Interestingly, the lengths of single-stranded DNA capable of relieving complex formation between the two proteins represent forms that might be introduced through repair and replicative events. Increasing p53 concentrations can also overcome the inhibition by steady-state levels of RP-A, potentially mimicking cellular points of balance. Finally, it has been shown previously that p53 can itself be stimulated for site-specific DNA binding when complexed through the C terminus with short single strands of DNA, and here we show that p53 stays bound to these short strands even after binding a physiologically relevant site. These results identify a potential dual role for single-stranded DNA in the regulation of DNA binding by p53 and give insights into the p53 response to DNA damage.

Published
1997
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