DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum.
DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). In vertebrates, the first step in NHEJ is recruitment of the DNA-dependent protein kinase (DNA-PK) to DNA termini. DNA-PK consists of a catalytic subunit (DNA-PKcs) that is re...
| Główni autorzy: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Język: | English |
| Wydane: |
2005
|
| _version_ | 1826278290250268672 |
|---|---|
| author | Hudson, J Hsu, D Guo, K Zhukovskaya, N Liu, P Williams, J Pears, C Lakin, N |
| author_facet | Hudson, J Hsu, D Guo, K Zhukovskaya, N Liu, P Williams, J Pears, C Lakin, N |
| author_sort | Hudson, J |
| collection | OXFORD |
| description | DNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). In vertebrates, the first step in NHEJ is recruitment of the DNA-dependent protein kinase (DNA-PK) to DNA termini. DNA-PK consists of a catalytic subunit (DNA-PKcs) that is recruited to DNA ends by the Ku70/Ku80 heterodimer. Although Ku has been identified in a wide variety of organisms, to date DNA-PKcs has only been identified experimentally in vertebrates. Here, we report the identification of DNA-PK in the nonvertebrate Dictyostelium. Dictyostelium Ku80 contains a conserved domain previously implicated in recruiting DNA-PKcs to DNA and consistent with this observation, we have identified DNA-PKcs in the Dictyostelium genome. Disruption of the gene encoding Dictyostelium DNA-PKcs results in sensitivity to DNA DSBs and defective H2AX phosphorylation in response to this form of DNA damage. However, these phenotypes are only apparent when DNA damage is administered in G(1) phase of the cell cycle. These data illustrate a cell cycle-dependent requirement for Dictyostelium DNA-PK in signaling and combating DNA DSBs and represent the first experimental verification of DNA-PKcs in a nonvertebrate organism. |
| first_indexed | 2024-03-06T23:41:44Z |
| format | Journal article |
| id | oxford-uuid:6f91a078-0cbe-4406-94db-b058bfdd7758 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:41:44Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:6f91a078-0cbe-4406-94db-b058bfdd77582022-03-26T19:31:22ZDNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6f91a078-0cbe-4406-94db-b058bfdd7758EnglishSymplectic Elements at Oxford2005Hudson, JHsu, DGuo, KZhukovskaya, NLiu, PWilliams, JPears, CLakin, NDNA double-strand breaks (DSBs) can be repaired by either homologous recombination (HR) or nonhomologous end-joining (NHEJ). In vertebrates, the first step in NHEJ is recruitment of the DNA-dependent protein kinase (DNA-PK) to DNA termini. DNA-PK consists of a catalytic subunit (DNA-PKcs) that is recruited to DNA ends by the Ku70/Ku80 heterodimer. Although Ku has been identified in a wide variety of organisms, to date DNA-PKcs has only been identified experimentally in vertebrates. Here, we report the identification of DNA-PK in the nonvertebrate Dictyostelium. Dictyostelium Ku80 contains a conserved domain previously implicated in recruiting DNA-PKcs to DNA and consistent with this observation, we have identified DNA-PKcs in the Dictyostelium genome. Disruption of the gene encoding Dictyostelium DNA-PKcs results in sensitivity to DNA DSBs and defective H2AX phosphorylation in response to this form of DNA damage. However, these phenotypes are only apparent when DNA damage is administered in G(1) phase of the cell cycle. These data illustrate a cell cycle-dependent requirement for Dictyostelium DNA-PK in signaling and combating DNA DSBs and represent the first experimental verification of DNA-PKcs in a nonvertebrate organism. |
| spellingShingle | Hudson, J Hsu, D Guo, K Zhukovskaya, N Liu, P Williams, J Pears, C Lakin, N DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum. |
| title | DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum. |
| title_full | DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum. |
| title_fullStr | DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum. |
| title_full_unstemmed | DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum. |
| title_short | DNA-PKcs-dependent signaling of DNA damage in Dictyostelium discoideum. |
| title_sort | dna pkcs dependent signaling of dna damage in dictyostelium discoideum |
| work_keys_str_mv | AT hudsonj dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT hsud dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT guok dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT zhukovskayan dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT liup dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT williamsj dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT pearsc dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum AT lakinn dnapkcsdependentsignalingofdnadamageindictyosteliumdiscoideum |