Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro
Human poly(ADP)-ribose polymerase-1 (PARP1) is a global regulator of various cellular processes, from DNA repair to gene expression. The underlying mechanism of PARP1 action during transcription remains unclear. Herein, we have studied the role of human PARP1 during transcription through nucleosomes...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/13/7107 |
| _version_ | 1797479726401454080 |
|---|---|
| author | Elena Y. Kotova Fu-Kai Hsieh Han-Wen Chang Natalia V. Maluchenko Marie-France Langelier John M. Pascal Donal S. Luse Alexey V. Feofanov Vasily M. Studitsky |
| author_facet | Elena Y. Kotova Fu-Kai Hsieh Han-Wen Chang Natalia V. Maluchenko Marie-France Langelier John M. Pascal Donal S. Luse Alexey V. Feofanov Vasily M. Studitsky |
| author_sort | Elena Y. Kotova |
| collection | DOAJ |
| description | Human poly(ADP)-ribose polymerase-1 (PARP1) is a global regulator of various cellular processes, from DNA repair to gene expression. The underlying mechanism of PARP1 action during transcription remains unclear. Herein, we have studied the role of human PARP1 during transcription through nucleosomes by RNA polymerase II (Pol II) in vitro. PARP1 strongly facilitates transcription through mononucleosomes by Pol II and displacement of core histones in the presence of NAD+ during transcription, and its NAD+-dependent catalytic activity is essential for this process. Kinetic analysis suggests that PARP1 facilitates formation of “open” complexes containing nucleosomal DNA partially uncoiled from the octamer and allowing Pol II progression along nucleosomal DNA. Anti-cancer drug and PARP1 catalytic inhibitor olaparib strongly represses PARP1-dependent transcription. The data suggest that the negative charge on protein(s) poly(ADP)-ribosylated by PARP1 interact with positively charged DNA-binding surfaces of histones transiently exposed during transcription, facilitating transcription through chromatin and transcription-dependent histone displacement/exchange. |
| first_indexed | 2024-03-09T21:50:58Z |
| format | Article |
| id | doaj.art-7b05caa5d0024687945a868b23e7b4b3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:50:58Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7b05caa5d0024687945a868b23e7b4b32023-11-23T20:08:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313710710.3390/ijms23137107Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In VitroElena Y. Kotova0Fu-Kai Hsieh1Han-Wen Chang2Natalia V. Maluchenko3Marie-France Langelier4John M. Pascal5Donal S. Luse6Alexey V. Feofanov7Vasily M. Studitsky8Fox Chase Cancer Center, Philadelphia, PA 19111, USADepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USAFox Chase Cancer Center, Philadelphia, PA 19111, USABiology Faculty, Lomonosov Moscow State University, 119234 Moscow, RussiaDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC H3T 1J4, CanadaDepartment of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, QC H3T 1J4, CanadaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USABiology Faculty, Lomonosov Moscow State University, 119234 Moscow, RussiaFox Chase Cancer Center, Philadelphia, PA 19111, USAHuman poly(ADP)-ribose polymerase-1 (PARP1) is a global regulator of various cellular processes, from DNA repair to gene expression. The underlying mechanism of PARP1 action during transcription remains unclear. Herein, we have studied the role of human PARP1 during transcription through nucleosomes by RNA polymerase II (Pol II) in vitro. PARP1 strongly facilitates transcription through mononucleosomes by Pol II and displacement of core histones in the presence of NAD+ during transcription, and its NAD+-dependent catalytic activity is essential for this process. Kinetic analysis suggests that PARP1 facilitates formation of “open” complexes containing nucleosomal DNA partially uncoiled from the octamer and allowing Pol II progression along nucleosomal DNA. Anti-cancer drug and PARP1 catalytic inhibitor olaparib strongly represses PARP1-dependent transcription. The data suggest that the negative charge on protein(s) poly(ADP)-ribosylated by PARP1 interact with positively charged DNA-binding surfaces of histones transiently exposed during transcription, facilitating transcription through chromatin and transcription-dependent histone displacement/exchange.https://www.mdpi.com/1422-0067/23/13/7107poly(ADP)-ribose polymerase-1PARP1nucleosometranscriptionelongationolaparib |
| spellingShingle | Elena Y. Kotova Fu-Kai Hsieh Han-Wen Chang Natalia V. Maluchenko Marie-France Langelier John M. Pascal Donal S. Luse Alexey V. Feofanov Vasily M. Studitsky Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro International Journal of Molecular Sciences poly(ADP)-ribose polymerase-1 PARP1 nucleosome transcription elongation olaparib |
| title | Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro |
| title_full | Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro |
| title_fullStr | Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro |
| title_full_unstemmed | Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro |
| title_short | Human PARP1 Facilitates Transcription through a Nucleosome and Histone Displacement by Pol II In Vitro |
| title_sort | human parp1 facilitates transcription through a nucleosome and histone displacement by pol ii in vitro |
| topic | poly(ADP)-ribose polymerase-1 PARP1 nucleosome transcription elongation olaparib |
| url | https://www.mdpi.com/1422-0067/23/13/7107 |
| work_keys_str_mv | AT elenaykotova humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT fukaihsieh humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT hanwenchang humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT nataliavmaluchenko humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT mariefrancelangelier humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT johnmpascal humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT donalsluse humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT alexeyvfeofanov humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro AT vasilymstuditsky humanparp1facilitatestranscriptionthroughanucleosomeandhistonedisplacementbypoliiinvitro |