A joint research group led by Changlin TIAN(High magnetic field laboratory, Chinese Academy of Sciences),Weimin GONG(Institute of Biophysics, Chinese Academy of Sciences), and Lei LI (The University of Texas MD Anderson Cancer Center)investigated the structure and function of Fanconi anemia (FA)-associated protein 24 (FAAP24).

Fanconi anemia (FA) is the result of a genetic defect in a cluster of proteins responsible for DNA repair. As a result, the majority of FA patients develop cancer, most often acute myelogenous leukemia, and 90% develop bone marrow failure (the inability to produce blood cells) by age 40. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Researchers solved the solution structures of the ERCC4 domain and (HhH)2domain of FAAP24 using high magnetic field NMR. Modeling of the FAAP24 structure indicates that FAAP24 may possess a high affinity toward single-stranded DNA (ssDNA). Testing of various FAAP24 mutations in vitroand in vivovalidated this prediction derived from structural analyses. It was found that the DNA-binding and FANCM-interacting functions of FAAP24, although both require the C-terminal (HhH)2domain, can be distinguished by segregation-of-function mutations. These results demonstrate dual roles of FAAP24 in DNA damage response against crosslinking lesions, one through the formation of FANCM/FAAP24 heterodimer and the other via its ssDNA-binding activity required in optimized checkpoint activation.

The research results entitled "Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response" was accepted by Cell Research and published online at September3rd, 2013 (DOI: 10.1038/cr.2013.124).

Relative link to this article:http://www.nature.com/cr/journal/vaop/ncurrent/full/cr2013124a.html