Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation.
Cellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation, with DSB complexity increasing with radiation ionization density. Using M059K and M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity, respectively), we investigated the repair of DNA damage, incl...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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2010
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| _version_ | 1797056256499777536 |
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| author | Anderson, J Harper, J Cucinotta, F O'Neill, P |
| author_facet | Anderson, J Harper, J Cucinotta, F O'Neill, P |
| author_sort | Anderson, J |
| collection | OXFORD |
| description | Cellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation, with DSB complexity increasing with radiation ionization density. Using M059K and M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity, respectively), we investigated the repair of DNA damage, including DSBs, induced by high- and low-LET radiation [gamma rays, alpha particles and high-charge and energy (HZE) ions]. In the absence of DNA-PKcs activity, less DSB repair and increased recruitment of RAD51 was seen at 24 h. After exposure to (56)Fe heavy ions, the number of cells with RAD51 tracks was less than the number of cells with gamma-H2AX at 24 h with both cell lines. Using alpha particles, comparable numbers of cells with visible gamma-H2AX and RAD51 were seen at 24 h in both cell lines. M059J cells irradiated with alpha particles accumulated in S phase, with a greater number of cyclin A and RAD51 co-stained cells seen at 24 h compared with M059K cells, where an S-phase block is absent. It is proposed that DNA-PKcs plays a role in the repair of some frank DSBs, which are longer-lived in NHEJ-deficient cells, and some non-DSB clustered damage sites that are converted into DSBs at replication as the cell cycles through to S phase. |
| first_indexed | 2024-03-06T19:20:48Z |
| format | Journal article |
| id | oxford-uuid:1a060da5-b178-45de-8a37-87dcd80a4544 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:20:48Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:1a060da5-b178-45de-8a37-87dcd80a45442022-03-26T10:52:21ZParticipation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1a060da5-b178-45de-8a37-87dcd80a4544EnglishSymplectic Elements at Oxford2010Anderson, JHarper, JCucinotta, FO'Neill, PCellular lesions (e.g. DSBs) are induced into DNA upon exposure to radiation, with DSB complexity increasing with radiation ionization density. Using M059K and M059J human glioblastoma cells (proficient and deficient in DNA-PKcs activity, respectively), we investigated the repair of DNA damage, including DSBs, induced by high- and low-LET radiation [gamma rays, alpha particles and high-charge and energy (HZE) ions]. In the absence of DNA-PKcs activity, less DSB repair and increased recruitment of RAD51 was seen at 24 h. After exposure to (56)Fe heavy ions, the number of cells with RAD51 tracks was less than the number of cells with gamma-H2AX at 24 h with both cell lines. Using alpha particles, comparable numbers of cells with visible gamma-H2AX and RAD51 were seen at 24 h in both cell lines. M059J cells irradiated with alpha particles accumulated in S phase, with a greater number of cyclin A and RAD51 co-stained cells seen at 24 h compared with M059K cells, where an S-phase block is absent. It is proposed that DNA-PKcs plays a role in the repair of some frank DSBs, which are longer-lived in NHEJ-deficient cells, and some non-DSB clustered damage sites that are converted into DSBs at replication as the cell cycles through to S phase. |
| spellingShingle | Anderson, J Harper, J Cucinotta, F O'Neill, P Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation. |
| title | Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation. |
| title_full | Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation. |
| title_fullStr | Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation. |
| title_full_unstemmed | Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation. |
| title_short | Participation of DNA-PKcs in DSB repair after exposure to high- and low-LET radiation. |
| title_sort | participation of dna pkcs in dsb repair after exposure to high and low let radiation |
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