Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint.
Human DNA polymerase (pol) λ functions in base excision repair and non-homologous end joining. We have previously shown that DNA pol λ is involved in accurate bypass of the two frequent oxidative lesions, 7,8-dihydro-8-oxoguanine and 1,2-dihydro-2-oxoadenine during the S phase. However, nothing is k...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797091624002519040 |
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| author | Zucca, E Bertoletti, F Wimmer, U Ferrari, E Mazzini, G Khoronenkova, S Grosse, N van Loon, B Dianov, G Hübscher, U Maga, G |
| author_facet | Zucca, E Bertoletti, F Wimmer, U Ferrari, E Mazzini, G Khoronenkova, S Grosse, N van Loon, B Dianov, G Hübscher, U Maga, G |
| author_sort | Zucca, E |
| collection | OXFORD |
| description | Human DNA polymerase (pol) λ functions in base excision repair and non-homologous end joining. We have previously shown that DNA pol λ is involved in accurate bypass of the two frequent oxidative lesions, 7,8-dihydro-8-oxoguanine and 1,2-dihydro-2-oxoadenine during the S phase. However, nothing is known so far about the relationship of DNA pol λ with the S phase DNA damage response checkpoint. Here, we show that a knockdown of DNA pol λ, but not of its close homologue DNA pol β, results in replication fork stress and activates the S phase checkpoint, slowing S phase progression in different human cancer cell lines. We furthermore show that DNA pol λ protects cells from oxidative DNA damage and also functions in rescuing stalled replication forks. Its absence becomes lethal for a cell when a functional checkpoint is missing, suggesting a DNA synthesis deficiency. Our results provide the first evidence, to our knowledge, that DNA pol λ is required for cell cycle progression and is functionally connected to the S phase DNA damage response machinery in cancer cells. |
| first_indexed | 2024-03-07T03:35:42Z |
| format | Journal article |
| id | oxford-uuid:bc36177b-d281-4e2e-8dba-53b2f63f3f1d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:35:42Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:bc36177b-d281-4e2e-8dba-53b2f63f3f1d2022-03-27T05:22:43ZSilencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bc36177b-d281-4e2e-8dba-53b2f63f3f1dEnglishSymplectic Elements at Oxford2013Zucca, EBertoletti, FWimmer, UFerrari, EMazzini, GKhoronenkova, SGrosse, Nvan Loon, BDianov, GHübscher, UMaga, GHuman DNA polymerase (pol) λ functions in base excision repair and non-homologous end joining. We have previously shown that DNA pol λ is involved in accurate bypass of the two frequent oxidative lesions, 7,8-dihydro-8-oxoguanine and 1,2-dihydro-2-oxoadenine during the S phase. However, nothing is known so far about the relationship of DNA pol λ with the S phase DNA damage response checkpoint. Here, we show that a knockdown of DNA pol λ, but not of its close homologue DNA pol β, results in replication fork stress and activates the S phase checkpoint, slowing S phase progression in different human cancer cell lines. We furthermore show that DNA pol λ protects cells from oxidative DNA damage and also functions in rescuing stalled replication forks. Its absence becomes lethal for a cell when a functional checkpoint is missing, suggesting a DNA synthesis deficiency. Our results provide the first evidence, to our knowledge, that DNA pol λ is required for cell cycle progression and is functionally connected to the S phase DNA damage response machinery in cancer cells. |
| spellingShingle | Zucca, E Bertoletti, F Wimmer, U Ferrari, E Mazzini, G Khoronenkova, S Grosse, N van Loon, B Dianov, G Hübscher, U Maga, G Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint. |
| title | Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint. |
| title_full | Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint. |
| title_fullStr | Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint. |
| title_full_unstemmed | Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint. |
| title_short | Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint. |
| title_sort | silencing of human dna polymerase λ causes replication stress and is synthetically lethal with an impaired s phase checkpoint |
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