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The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.

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Title: The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.
Authors: Morris, Joanna R., Boutell, Chris, Keppler, Melanie, Densham, Ruth, Weekes, Daniel, Alamshah, Amin, Butler, Laura, Galanty, Yaron, Pangon, Laurent, Kiuchi, Tai, Ng, Tony, Solomon, Ellen
Source: Nature. 12/17/2009, Vol. 462 Issue 7275, p886-890. 5p. 4 Graphs.
Subjects: Genetic toxicology, BRCA genes, Tumor suppressor genes, DNA damage, Breast cancer, Ovarian cancer, Ubiquitin, Ligases, Enzymes
Abstract: Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress.
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  Data: <searchLink fieldCode="AR" term="%22Morris%2C+Joanna+R%2E%22">Morris, Joanna R.</searchLink><br /><searchLink fieldCode="AR" term="%22Boutell%2C+Chris%22">Boutell, Chris</searchLink><br /><searchLink fieldCode="AR" term="%22Keppler%2C+Melanie%22">Keppler, Melanie</searchLink><br /><searchLink fieldCode="AR" term="%22Densham%2C+Ruth%22">Densham, Ruth</searchLink><br /><searchLink fieldCode="AR" term="%22Weekes%2C+Daniel%22">Weekes, Daniel</searchLink><br /><searchLink fieldCode="AR" term="%22Alamshah%2C+Amin%22">Alamshah, Amin</searchLink><br /><searchLink fieldCode="AR" term="%22Butler%2C+Laura%22">Butler, Laura</searchLink><br /><searchLink fieldCode="AR" term="%22Galanty%2C+Yaron%22">Galanty, Yaron</searchLink><br /><searchLink fieldCode="AR" term="%22Pangon%2C+Laurent%22">Pangon, Laurent</searchLink><br /><searchLink fieldCode="AR" term="%22Kiuchi%2C+Tai%22">Kiuchi, Tai</searchLink><br /><searchLink fieldCode="AR" term="%22Ng%2C+Tony%22">Ng, Tony</searchLink><br /><searchLink fieldCode="AR" term="%22Solomon%2C+Ellen%22">Solomon, Ellen</searchLink>
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  Data: <searchLink fieldCode="DE" term="%22Genetic+toxicology%22">Genetic toxicology</searchLink><br /><searchLink fieldCode="DE" term="%22BRCA+genes%22">BRCA genes</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+suppressor+genes%22">Tumor suppressor genes</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+damage%22">DNA damage</searchLink><br /><searchLink fieldCode="DE" term="%22Breast+cancer%22">Breast cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Ovarian+cancer%22">Ovarian cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Ubiquitin%22">Ubiquitin</searchLink><br /><searchLink fieldCode="DE" term="%22Ligases%22">Ligases</searchLink><br /><searchLink fieldCode="DE" term="%22Enzymes%22">Enzymes</searchLink>
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  Data: Mutations in BRCA1 are associated with a high risk of breast and ovarian cancer. BRCA1 participates in the DNA damage response and acts as a ubiquitin ligase. However, its regulation remains poorly understood. Here we report that BRCA1 is modified by small ubiquitin-like modifier (SUMO) in response to genotoxic stress, and co-localizes at sites of DNA damage with SUMO1, SUMO2/3 and the SUMO-conjugating enzyme Ubc9. PIAS SUMO E3 ligases co-localize with and modulate SUMO modification of BRCA1, and are required for BRCA1 ubiquitin ligase activity in cells. In vitro SUMO modification of the BRCA1/BARD1 heterodimer greatly increases its ligase activity, identifying it as a SUMO-regulated ubiquitin ligase (SRUbL). Further, PIAS SUMO ligases are required for complete accumulation of double-stranded DNA (dsDNA) damage-repair proteins subsequent to RNF8 accrual, and for proficient double-strand break repair. These data demonstrate that the SUMOylation pathway plays a significant role in mammalian DNA damage response. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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