Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage
The endoribonuclease Dicer is a key component of the human RNA interference pathway and is known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical Dicer generates small noncoding RNA to mediate the DNA damage response (DDR). Here, we show that human Dicer is...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Published: |
Rockefeller University Press
2017
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| _version_ | 1797050582038478848 |
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| author | Burger, K Schlackow, M Potts, M Hester, S Mohammed, S Gullerova, M |
| author_facet | Burger, K Schlackow, M Potts, M Hester, S Mohammed, S Gullerova, M |
| author_sort | Burger, K |
| collection | OXFORD |
| description | The endoribonuclease Dicer is a key component of the human RNA interference pathway and is known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical Dicer generates small noncoding RNA to mediate the DNA damage response (DDR). Here, we show that human Dicer is phosphorylated in the platform–Piwi/Argonaute/Zwille–connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks. We further demonstrate that turnover of damage-induced nuclear, double-stranded (ds) RNA requires additional phosphorylation of carboxy-terminal Dicer residues (S1728 and S1852). DNA damage-induced nuclear Dicer accumulation is conserved in mammals. Dicer depletion causes endogenous DNA damage and delays the DDR by impaired recruitment of repair factors MDC1 and 53BP1. Collectively, we place Dicer within the context of the DDR by demonstrating a DNA damage-inducible phosphoswitch that causes localized processing of nuclear dsRNA by p-Dicer to promote DNA repair. |
| first_indexed | 2024-03-06T18:07:17Z |
| format | Journal article |
| id | oxford-uuid:01dc304a-e2f7-46cc-bd48-31cc0f124ef8 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:07:17Z |
| publishDate | 2017 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | oxford-uuid:01dc304a-e2f7-46cc-bd48-31cc0f124ef82022-03-26T08:37:16ZNuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damageJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:01dc304a-e2f7-46cc-bd48-31cc0f124ef8Symplectic Elements at OxfordRockefeller University Press2017Burger, KSchlackow, MPotts, MHester, SMohammed, SGullerova, MThe endoribonuclease Dicer is a key component of the human RNA interference pathway and is known for its role in cytoplasmic microRNA production. Recent findings suggest that noncanonical Dicer generates small noncoding RNA to mediate the DNA damage response (DDR). Here, we show that human Dicer is phosphorylated in the platform–Piwi/Argonaute/Zwille–connector helix cassette (S1016) upon induction of DNA damage. Phosphorylated Dicer (p-Dicer) accumulates in the nucleus and is recruited to DNA double-strand breaks. We further demonstrate that turnover of damage-induced nuclear, double-stranded (ds) RNA requires additional phosphorylation of carboxy-terminal Dicer residues (S1728 and S1852). DNA damage-induced nuclear Dicer accumulation is conserved in mammals. Dicer depletion causes endogenous DNA damage and delays the DDR by impaired recruitment of repair factors MDC1 and 53BP1. Collectively, we place Dicer within the context of the DDR by demonstrating a DNA damage-inducible phosphoswitch that causes localized processing of nuclear dsRNA by p-Dicer to promote DNA repair. |
| spellingShingle | Burger, K Schlackow, M Potts, M Hester, S Mohammed, S Gullerova, M Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
| title | Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
| title_full | Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
| title_fullStr | Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
| title_full_unstemmed | Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
| title_short | Nuclear phosphorylated Dicer processes double-stranded RNA in response to DNA damage |
| title_sort | nuclear phosphorylated dicer processes double stranded rna in response to dna damage |
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