Related Experiment Video
Updated: Jul 7, 2026
08:53
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response
Bin Wang1, Shuhei Matsuoka, Bryan A Ballif
1Department of Genetics, Center for Genetics and Genomics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Science (New York, N.Y.)
|May 26, 2007
Summary
Researchers discovered Abraxas, a protein that binds to BRCA1 and helps recruit RAP80. This complex is crucial for DNA damage resistance, cell cycle control, and DNA repair, aiding BRCA1
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- The BRCA1 protein's BRCT repeats are vital for tumor suppression.
- Understanding BRCA1 interactions is key to cancer predisposition and treatment.
Purpose of the Study:
- To identify novel proteins interacting with BRCA1's BRCT repeats.
- To elucidate the function of these interactions in DNA damage response.
Main Methods:
- Phosphopeptide affinity proteomic analysis to identify binding partners.
- Co-immunoprecipitation and focus formation assays to study protein complex formation and localization.
Main Results:
- Abraxas directly binds BRCA1's BRCT repeats via a specific phospho-motif.
- Abraxas forms a distinct BRCA1 complex, excluding BACH1 and CtIP.
- Abraxas recruits RAP80 to BRCA1, forming a complex essential for DNA damage resistance, G(2)-M checkpoint control, and DNA repair.
- RAP80 facilitates BRCA1 accumulation at DNA damage sites, partly through ubiquitinated protein recognition.
Conclusions:
- The Abraxas-RAP80 complex is a novel component of the BRCA1 pathway.
- This complex plays a critical role in cellular responses to DNA damage.
- Targeting this complex could offer new therapeutic strategies for BRCA1-related cancers.
More Related Videos
Related Concept Videos
01:54Base Excision Repair
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
01:02Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:31Homologous Recombination
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...