RAP80 Targets BRCA1 to Specific Ubiquitin Structures at DNA Damage Sites

By B. Sobhian, G. Shao, Dana R. Lilli, A. Culhane, L. Moreau, B. Xia, D. Livingston, R. Greenberg. Science, 2007

708 citations recorded by the source corpus.

Mutations affecting the BRCT domains of the breast cancer–associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-γH2AX–dependent lysine6- and lysine63-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/9169db9e2a77b3a957ce448a1b6069031532c023

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In Molecular Biology

1. Stephen P. Jackson
2. J. Bartek
3. J. Lukas
4. S. Polo
5. M. Jasin
6. L. Zou
7. Alexandre Maréchal
8. J. R. Chapman

In Oncology

1. Stephen P. Jackson
2. J. Bartek
3. J. Lukas
4. S. Polo
5. L. Zou
6. Alexandre Maréchal
7. J. R. Chapman
8. M. Foiani

Citations in the corpus

• RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. (2007, background): “Together, our study implicates RNF8 as a novel DNA-damage-responsive protein that integrates protein phosphorylation and ubiquitylation signaling and plays a critical role in the cellular response to genotoxic stress.”
• RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. (2007, positive): “Finally, chromatin retention of BRCA1 is also regulated by MDC1 (Bekker-Jensen et al., 2006; Lou et al., 2003) and requires at least two additional proteins, RAP80 and ABRA1 (Kim et al., 2007; Sobhian et al., 2007; Wang et al., 2007; Yan et al., 2007).”
• An ATM-Dependent Transcriptional Silencing Program is Transmitted Through Chromatin in Cis to DNA Double Strand Breaks (2010, methodology): “…Cell 141, 970–981, June 11, 2010 ª2010 Elsevier Inc. specific for K63- and K48-conjugated polyubiquitin (Newton et al., 2008), we also detected an enrichment of K63Ub, but not K48Ub, consistent with previous reports (Figure 5D) (Doil et al., 2009; Sob- hian et al., 2007; Stewart et al., 2009).”
• Playing the end game: DNA double-strand break repair pathway choice. (2012, background): “…that BRCA1 performs a ubiquitin-editing function independent of its E3-Ub ligase activity: BRCA1 interacts with two deubiquinating (DUB) enzymes, BAP1 and BRCC36 (Table 1), via RING- and Rap80-mediated interactions, respectively (Chen et al., 2006; Jensen et al., 1998; Sobhian et al., 2007).”
• Homologous recombination and human health: the roles of BRCA1, BRCA2 and associated proteins (2015, background): “In addition to BRCA1, Abraxas binds to another component of the BRCA1-A complex RAP80, which recognizes polyubiquitylated histones like H2AX to recruit the BRCA1-A complex to DNA-damage sites (Kim et al. 2007; Sobhian et al. 2007; Wang et al. 2007).”
• Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. (2011, background): “While such motifs have been identified in the BRCA1-associated protein RAP80 (receptor-associated protein 80) (H Kim et al. 2007; Sobhian et al. 2007; Sato et al. 2009; Sims and Cohen 2009), the ubiquitin ligase RNF168 (Doil et al. 2009; Pinato et al. 2009, 2011; Stewart et al. 2009), and the RAD18…”
• RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. (2012, background): “…to the ubiquitindependent signals necessary for the further recruitment of downstream regulators of the DSB response pathway, such as 53BP1 and the BRCA1 complex (Al-Hakim et al., 2010; Kim et al., 2007; Panier and Durocher, 2009; Sobhian et al., 2007; Wang et al., 2002; Yan et al., 2007).”
• Ubiquitin-binding domains — from structures to functions (2009, background): “For example, receptor associated protein 80 (RAP80; also known as UIMC1) targets BRCA1 to DNA damage-induced foc”
• DNA damage sensing by the ATM and ATR kinases. (2013, background): “3B) (Huen et al. 2007; Kim et al. 2007a,b; Kolas et al. 2007; Mailand et al. 2007; Sobhian et al. 2007; Wang and Elledge 2007; Wang et al. 2007; Doil et al. 2009; Galanty et al. 2009; Morris et al. 2009; Stewart 2009; Bekker-Jensen et al. 2010; Meerang et al. 2011; Mattiroli et al. 2012).”