The SH3 domain of αII spectrin is a target for the fanconi anemia protein, FANCG

Joel A. Lefferts, Chuan Wang, Deepa Sridharan, Melissa Baralt, Muriel W. Lambert

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


The structural protein nonerythroid α spectrin (αIISp) plays a role in the repair of DNA interstrand cross-links and is deficient in cells from patients with Fanconi anemia (FA), in which there is a defect in ability to repair such cross-links. We have proposed a model in which αIISp, whose stability is dependent on FA proteins, acts as a scaffold to aid in recruitment of repair proteins to sites of damage. In order to get a clearer understanding of the proposed role of FA proteins in maintaining stability of αIISp, yeast two-hybrid analysis was carried out to determine whether FA proteins directly interact with αIISp and, if so, to map the sites of interaction. Four overlapping regions of αIISp were constructed. FANCG interacted with one of these regions and specifically with the SH3 domain in this region of αIISp. The site of interaction in FANCG was mapped to a motif that binds to SH3 domains and contains a consensus sequence with preference for the SH3 domain of αIISp. This site of interaction was confirmed using site-directed mutagenesis. Two FA proteins that did not contain motifs that bind to SH3 domains, FANCC and FANCF, did not interact with the SH3 domain of αIISp. These results demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the SH3 domain of αIISp. We propose that this binding of FANCG to αIISp may be important for the stability of αIISp in cells and the role αIISp plays in the DNA repair process.

Original languageEnglish (US)
Pages (from-to)254-263
Number of pages10
Issue number2
StatePublished - Jan 20 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry


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