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PMID:19261746

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Citation

Shao, G, Patterson-Fortin, J, Messick, TE, Feng, D, Shanbhag, N, Wang, Y and Greenberg, RA (2009) MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks. Genes Dev. 23:740-54

Abstract

Rap80 targets the breast cancer suppressor protein BRCA1 along with Abraxas and the BRCC36 deubiquitinating enzyme (DUB) to polyubiquitin structures at DNA double-strand breaks (DSBs). These DSB targeting events are essential for BRCA1-dependent DNA damage response-induced checkpoint and repair functions. Here, we identify MERIT40 (Mediator of Rap80 Interactions and Targeting 40 kD)/(C19orf62) as a Rap80-associated protein that is essential for BRCA1-Rap80 complex protein interactions, stability, and DSB targeting. Moreover, MERIT40 is required for Rap80-associated lysine(63)-ubiquitin DUB activity, a critical component of BRCA1-Rap80 G2 checkpoint and viability responses to ionizing radiation. Thus, MERIT40 represents a novel factor that links BRCA1-Rap80 complex integrity, DSB recognition, and ubiquitin chain hydrolytic activities to the DNA damage response. These findings provide new molecular insights into how BRCA1 associates with independently assembled core protein complexes to maintain genome integrity.

Links

PubMed PMC2661612 Online version:10.1101/gad.1739609

Keywords

Adaptor Proteins, Signal Transducing; BRCA1 Protein/metabolism; Carrier Proteins/genetics; Carrier Proteins/metabolism; Carrier Proteins/physiology; Cell Cycle/physiology; Cell Cycle/radiation effects; Cell Line, Tumor; DNA Breaks, Double-Stranded; DNA Repair/physiology; Humans; Nuclear Proteins/metabolism; Protein Binding; Ubiquitin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BRCC3

involved_in

GO:0007095: mitotic G2 DNA damage checkpoint signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRCC3

involved_in

GO:0006302: double-strand break repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRCC3

involved_in

GO:0010212: response to ionizing radiation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRCC3

part_of

GO:0070531: BRCA1-A complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BRCC3

enables

GO:0008237: metallopeptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:BRCC3

enables

GO:0140492: metal-dependent deubiquitinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:BRCC3

involved_in

GO:0045739: positive regulation of DNA repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BRCC3

involved_in

GO:0070537: histone H2A K63-linked deubiquitination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ABRX1

part_of

GO:0070531: BRCA1-A complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BABA1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BABA1

involved_in

GO:0007095: mitotic G2 DNA damage checkpoint signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BABA1

involved_in

GO:0006302: double-strand break repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BABA1

part_of

GO:0070531: BRCA1-A complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:BABA1

involved_in

GO:0045739: positive regulation of DNA repair

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BABA1

involved_in

GO:0070536: protein K63-linked deubiquitination

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BABA2

part_of

GO:0070531: BRCA1-A complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:UIMC1

part_of

GO:0070531: BRCA1-A complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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