Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage.
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Abstract | BRCA1 is a breast and ovarian tumor suppressor. Given its numerous incompletely understood functions and the possibility that more exist, we performed complementary systematic screens in search of new BRCA1 protein-interacting partners. New BRCA1 functions and/or a better understanding of existing ones were sought. Among the new interacting proteins identified, genetic interactions were detected between BRCA1 and four of the interactors: TONSL, SETX, TCEANC, and TCEA2. Genetic interactions were also detected between BRCA1 and certain interactors of TONSL, including both members of the FACT complex. From these results, a new BRCA1 function in the response to transcription-associated DNA damage was detected. Specifically, new roles for BRCA1 in the restart of transcription after UV damage and in preventing or repairing damage caused by stabilized R loops were identified. These roles are likely carried out together with some of the newly identified interactors. This new function may be important in BRCA1 tumor suppression, since the expression of several interactors, including some of the above-noted transcription proteins, is repeatedly aberrant in both breast and ovarian cancers. |
Year of Publication | 2014
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Journal | Genes Dev
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Volume | 28
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Issue | 17
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Pages | 1957-75
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Date Published | 2014 Sep 01
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ISSN | 1549-5477
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URL | |
DOI | 10.1101/gad.241620.114
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PubMed ID | 25184681
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PubMed Central ID | PMC4197947
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Grant list | DP1 GM105378 / GM / NIGMS NIH HHS / United States
F30 CA167895 / CA / NCI NIH HHS / United States
P50CA089393 / CA / NCI NIH HHS / United States
P01 CA080111 / CA / NCI NIH HHS / United States
R01 HG001715 / HG / NHGRI NIH HHS / United States
1F30CA167895-01 / CA / NCI NIH HHS / United States
P50 CA089393 / CA / NCI NIH HHS / United States
R01 CA136512 / CA / NCI NIH HHS / United States
P01CA080111 / CA / NCI NIH HHS / United States
R01CA136512 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
U54CA112962 / CA / NCI NIH HHS / United States
U01 HG001715 / HG / NHGRI NIH HHS / United States
R01HG001715 / HG / NHGRI NIH HHS / United States
P01 NS047572 / NS / NINDS NIH HHS / United States
DP1 GM105378 / DP / NCCDPHP CDC HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
P01NS047572 / NS / NINDS NIH HHS / United States
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