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I know that BRCA2 interacts with RAD51 to repair DNA damage.

But how exactly does it function ? What are the other proteins that interact with it ?

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2 Answers 2

up vote 3 down vote accepted

I'm just skimming through it now, but this 2011 review in Nature Reviews Cancer looks like it has everything you could possibly want to know about the BRCA1/BRCA2 pathway. If you don't have access to the journal, the first page of this Google search should have a PDF link to Researchgate down near the bottom, or you can try this direct link.

I apologize for the "link-only" answer, but there is a ton of info in the paper, and it would be rather difficult to summarize it in just a few paragraphs. This is a rather broad question, so perhaps you could read through the review and references, and if you still have specific questions about the pathways or interactions you can ask another question.

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I agree with you, this paper offers a very good overview. –  Chris Mar 18 at 18:39

enter image description here

Here is an image of BRCA2 and RAD51 oriented.( I produced this using PyMOL!)

The chocolate coloured part is some BRCA repeats. You can see how BRCA repeats and RAD51 are oriented. Here, the association is shown only for one of the 7 subunits of RAD51

The exact mechanism in brief : .

enter image description here

  1. BRCA2 binds to RAD51 subunits within the ring via BRC repeat mimicry of the RAD51 polymerization motif.

2.BRC repeats disassembles the ring.

3.The RAD51:BRCA2 comple is recruited to a DNA double strand break.

4.BRCA2 helps displace a protective protein, Replication protein A- RPA, and binds the primary ssDNA substrate by its B folds.

5.It loads RAD51 onto DNA. The handoff reaction might be facilitated by attraction of DNA by the positively charged BRC repeat helical arches.The BRCA2 helix-turn-helix domain(red) at the end of the tower may bind dsDNA in cis at the ssDNA/dsDNA intra-DNA junction (3) or in trans to the dsDNA that later serves as the homologous DNA template (6) and the positively charged arch may also help to attract the dsDNA template.

Source : Yang etal. 2002 , Shin et al 2003

Thanks to Nicholas Provert for teaching me basics of PyMOL on Coursera.

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