The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair

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The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair

The protein product of the breast and ovarian cancer gene, BRCA1, is part of an obligate heterodimer with BARD1. Together these RING bearing proteins act as an E3 ubiquitin ligase. Several functions have been attributed to BRCA1 that contribute to genome integrity but which of these, if any, require this enzymatic function was unclear. Here we review recent studies clarifying the role of BRCA1 ...

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BRCA1 Is a Histone-H2A-Specific Ubiquitin Ligase

The RING domain proteins BRCA1 and BARD1 comprise a heterodimeric ubiquitin (E3) ligase that is required for the accumulation of ubiquitin conjugates at sites of DNA damage and for silencing at DNA satellite repeat regions. Despite its links to chromatin, the substrate and underlying function of the BRCA1/BARD1 ubiquitin ligase remain unclear. Here, we show that BRCA1/BARD1 specifically ubiquit...

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A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation, CHK1 Activation, and DNA Repair

BACKGROUND The breast and ovarian cancer suppressor BRCA1 is essential for cellular responses to DNA damage. It heterodimerizes with BARD1 to acquire an E3 ubiquitin (Ub) ligase activity that is often compromised by cancer-associated mutations. Neither the significance of this activity to damage responses, nor a relevant in vivo substrate, is clear. RESULTS We have separated DNA-damage respon...

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Down-regulation of BRCA1-BARD1 ubiquitin ligase by CDK2.

BRCA1, a breast and ovarian tumor suppressor, is a phosphoprotein whose cellular expression level is regulated in a cell cycle-dependent manner. BRCA1 interacts with BARD1 to generate significant ubiquitin ligase activity which catalyzes nontraditional Lys-6-linked polyubiquitin chains. However, it is not clear how the activity is regulated and how this affects BRCA1's multiple cellular functio...

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Estrogen receptor is a putative substrate for the BRCA1 ubiquitin ligase

The breast cancer suppressor protein, BRCA1, is a ubiquitin ligase expressed in a wide range of tissues. However, inheritance of a single BRCA1 mutation significantly increases a woman’s lifetime chance of developing tissue-specific cancers in the breast and ovaries. Recently, studies have suggested this tissue specificity may be linked to inhibition of estrogen receptor (ER ) transcriptional a...

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ژورنال

عنوان ژورنال: Nucleus

سال: 2017

ISSN: 1949-1034,1949-1042

DOI: 10.1080/19491034.2016.1267092