Ubiquitin-Binding Protein RAP80 Mediates BRCA1-Dependent DNA Damage Response

  title={Ubiquitin-Binding Protein RAP80 Mediates BRCA1-Dependent DNA Damage Response},
  author={Hongtae Kim and Junjie Chen and Xiaochun Yu},
  pages={1202 - 1205}
Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of breast and ovarian cancers. BRCA1 participates in the cellular DNA damage response. We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo. Moreover, RAP80 specifically… 

CCDC98 targets BRCA1 to DNA damage sites

It is demonstrated that CCDC98 is a BRCA1 binding partner that mediates BrcA1 function in response to DNA damage.

CCDC98 is a BRCA1-BRCT domain–binding protein involved in the DNA damage response

Results suggest that CCDC98 is a mediator of BRCA1 function involved in the mammalian DNA damage response, and has a role in radiation sensitivity and damage-induced G2/M checkpoint control.

BRCA1 and DNA damage response

The various mechanisms of PARP inhibitors’ resistance in tumors with BRCA1 mutated are summarized and the function and its involvement in the regulation of DNA damage response network is described.

The role of BRCA1 in DNA damage response

Recent advances regarding the understanding of the role of BRCA1 in tumor suppression and DNA damage response are discussed, including DNA damage-induced cell cycle checkpoint activation andDNA damage repair.

BRCA1 and BRCA2: Role in the DNA Damage Response, Cancer Formation and Treatment

This chapter will discuss the functions of these proteins and how they relate to tumour development, and therapy.

The role of BRCA 1 in DNA damage response

Recent advances regarding the understanding of the role of BRCA1 in tumor suppression and DNA damage response are discussed, including DNA damage-induced cell cycle checkpoint activation andDNA damage repair.

MERIT40 facilitates BRCA1 localization and DNA damage repair.

This study reveals that a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization.

New players in the BRCA1-mediated DNA damage responsive pathway.

A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway, including RNF8, RAP80 and CCDC98, that work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRC a1 function in G2/M checkpoint control.



BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.

It is demonstrated that BRCA1 Ring domain catalyzes CtIP ubiquitination in a manner that depends on a phosphorylation-mediated interaction between CtIP and B RCA1 BRCT domains, and proposed that BrcA1 can regulate the functions of its substrates through nonproteasomal pathways that do not involve substrate degradation.

Roles of BRCA1 and its interacting proteins

  • C. DengS. Brodie
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2000
This review examines the understanding of the significance of the interactions between BRCA1 and other proteins, through which BRCa1 maintains genome integrity and represses tumor formation.

BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage

It is concluded that BRCA1 regulates key effectors that control the G2/M checkpoint and is therefore involved in regulating the onset of mitosis.

DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal Domains

It is demonstrated here that a CTBP-interacting protein CtIP interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner, which implicate CtIP as a critical player in cell cycle checkpoint control and provides molecular mechanisms by which BRC a1 controls multiple cell cycle transitions after DNA damage.

Functional Interaction of Monoubiquitinated FANCD2 and BRCA2/FANCD1 in Chromatin

Results demonstrate that monoubiquitination of FANCD2, which is regulated by the FA pathway, promotes BRCA2 loading into chromatin complexes, which appear to be required for normal homology-directed DNA repair.

The RING Heterodimer BRCA1-BARD1 Is a Ubiquitin Ligase Inactivated by a Breast Cancer-derived Mutation*

The results suggest that the BRCA1-BARD1 complex contains a ubiquitin ligase activity that is important in prevention of breast and ovarian cancer development.

Autoubiquitination of the BRCA1·BARD1 RING Ubiquitin Ligase*

It is reported that co-expression of BRCA1-(1–639) and BARD1 in bacteria can assemble a potent ubiquitin ligase activity, raising the possibility that BRC a·BARD1 acts to assemble non-lysine 48-linked polyubiquitin chains that may serve as part of a signaling platform required for coordinating DNA repair-related events.

Involvement of Brca1 in S-Phase and G2-Phase Checkpoints after Ionizing Irradiation

The results clarify the checkpoint roles for each of these three gene products, demonstrate that control of cell cycle arrests must now be included among the important functions of Brca1 in cellular responses to DNA damage, and suggest that Atm phosphorylation of BrCA1 is required for the G2/M checkpoint.

The human decatenation checkpoint

Results imply that ATR and BRCA1 enforce the decatenation G2 checkpoint, which may act to exclude cyclin B1/Cdk1 complexes from the nucleus.