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BRCA1 Forms a Functional Complex with γ-H2AX as a Late Response to Genotoxic Stress
Joint Authors
Dalugdugan, Esther de la Rosa
Miranda-Carboni, Gustavo A.
Lane, Timothy F.
Krum, Susan A.
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-09-27
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Following genotoxic stress, the histone H2AX becomes phosphorylated at serine 139 by the ATM/ATR family of kinases.
The tumor suppressor BRCA1, also phosphorylated by ATM/ATR kinases, is one of several proteins that colocalize with phospho-H2AX (γ-H2AX) at sites of active DNA repair.
Both the precise mechanism and the purpose of BRCA1 recruitment to sites of DNA damage are unknown.
Here we show that BRCA1 and γ-H2AX form an acid-stable biochemical complex on chromatin after DNA damage.
Maximal association of BRCA1 with γ-H2AX correlates with reduced global γ-H2AX levels on chromatin late in the repair process.
Since BRCA1 is known to have E3 ubiquitin ligase activity in vitro, we examined H2AX for evidence of ubiquitination.
We found that H2AX is ubiquitinated at lysines 119 and 119 in vivo and that blockage of 26S proteasome function stabilizes γ-H2AX levels within cells.
When BRCA1 levels were reduced, ubiquitination of H2AX was also reduced, and the cells retained higher levels of phosphorylated H2AX.
These results indicate that BRCA1 is recruited into stable complexes with γ-H2AX and that the complex is involved in attenuation of the γ-H2AX repair signal after DNA damage.
American Psychological Association (APA)
Krum, Susan A.& Dalugdugan, Esther de la Rosa& Miranda-Carboni, Gustavo A.& Lane, Timothy F.. 2010. BRCA1 Forms a Functional Complex with γ-H2AX as a Late Response to Genotoxic Stress. Journal of Nucleic Acids،Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-499135
Modern Language Association (MLA)
Krum, Susan A.…[et al.]. BRCA1 Forms a Functional Complex with γ-H2AX as a Late Response to Genotoxic Stress. Journal of Nucleic Acids No. 2010 (2010), pp.1-9.
https://search.emarefa.net/detail/BIM-499135
American Medical Association (AMA)
Krum, Susan A.& Dalugdugan, Esther de la Rosa& Miranda-Carboni, Gustavo A.& Lane, Timothy F.. BRCA1 Forms a Functional Complex with γ-H2AX as a Late Response to Genotoxic Stress. Journal of Nucleic Acids. 2010. Vol. 2010, no. 2010, pp.1-9.
https://search.emarefa.net/detail/BIM-499135
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-499135