Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks.
DNA double strand breaks (DSBs) are amongst the most deleterious lesions induced within the cell following exposure to ionizing radiation. Mammalian cells repair these breaks predominantly via the nonhomologous end joining pathway which is active throughout the cell cycle and is error prone. The alt...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2008
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| _version_ | 1797064087243325440 |
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| author | Harper, J Reynolds, P Leatherbarrow, E Botchway, S Parker, A O'Neill, P |
| author_facet | Harper, J Reynolds, P Leatherbarrow, E Botchway, S Parker, A O'Neill, P |
| author_sort | Harper, J |
| collection | OXFORD |
| description | DNA double strand breaks (DSBs) are amongst the most deleterious lesions induced within the cell following exposure to ionizing radiation. Mammalian cells repair these breaks predominantly via the nonhomologous end joining pathway which is active throughout the cell cycle and is error prone. The alternative pathway for repair of DSBs is homologous recombination (HR) which is error free and active during S- and G2/M-phases of the cell cycle. We have utilized near-infrared laser radiation to induce DNA damage in individual mammalian cells through multiphoton excitation processes to investigate the dynamics of single cell DNA damage processing. We have used immunofluorescent imaging of gamma-H2AX (a marker for DSBs) in mammalian cells and investigated the colocalization of this protein with ATM, p53 binding protein 1 and RAD51, an integral protein of the HR DNA repair pathway. We have observed persistent DSBs at later times postlaser irradiation which are indicative of DSBs arising at replication, presumably from UV photoproducts or clustered damage containing single strand breaks. Cell cycle studies have shown that in G1 cells, a significant fraction of multiphoton laser-induced prompt DSBs persists for > 4 h in addition to those induced at replication. |
| first_indexed | 2024-03-06T21:09:12Z |
| format | Journal article |
| id | oxford-uuid:3d8f1e10-c81f-45bd-ba7d-a4e755cd7e2e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:09:12Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:3d8f1e10-c81f-45bd-ba7d-a4e755cd7e2e2022-03-26T14:20:07ZInduction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3d8f1e10-c81f-45bd-ba7d-a4e755cd7e2eEnglishSymplectic Elements at Oxford2008Harper, JReynolds, PLeatherbarrow, EBotchway, SParker, AO'Neill, PDNA double strand breaks (DSBs) are amongst the most deleterious lesions induced within the cell following exposure to ionizing radiation. Mammalian cells repair these breaks predominantly via the nonhomologous end joining pathway which is active throughout the cell cycle and is error prone. The alternative pathway for repair of DSBs is homologous recombination (HR) which is error free and active during S- and G2/M-phases of the cell cycle. We have utilized near-infrared laser radiation to induce DNA damage in individual mammalian cells through multiphoton excitation processes to investigate the dynamics of single cell DNA damage processing. We have used immunofluorescent imaging of gamma-H2AX (a marker for DSBs) in mammalian cells and investigated the colocalization of this protein with ATM, p53 binding protein 1 and RAD51, an integral protein of the HR DNA repair pathway. We have observed persistent DSBs at later times postlaser irradiation which are indicative of DSBs arising at replication, presumably from UV photoproducts or clustered damage containing single strand breaks. Cell cycle studies have shown that in G1 cells, a significant fraction of multiphoton laser-induced prompt DSBs persists for > 4 h in addition to those induced at replication. |
| spellingShingle | Harper, J Reynolds, P Leatherbarrow, E Botchway, S Parker, A O'Neill, P Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks. |
| title | Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks. |
| title_full | Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks. |
| title_fullStr | Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks. |
| title_full_unstemmed | Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks. |
| title_short | Induction of persistent double strand breaks following multiphoton irradiation of cycling and G1-arrested mammalian cells-replication-induced double strand breaks. |
| title_sort | induction of persistent double strand breaks following multiphoton irradiation of cycling and g1 arrested mammalian cells replication induced double strand breaks |
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