Characterisation of a novel gene with a potential role in the Fanconi anaemia tumour suppressor pathway

[摘要] PFAP (putative Fanconi Anaemia protein) is a novel uncharacterised protein, whose functions till date remains elusive. According to unpublished results from our laboratory, cells lacking PFAP resemble loss of phenotypes as seen with cells lacking known Fanconi anaemia proteins.Fanconi anaemia proteins are important in the repair of inter-strand crosslinks (ICLs) and the maintenance of genome instability. Based on two reports, there is a possibility of PFAP playing a key role in regulating histone lysine methylation, via its interaction with the SET/COMPASS like histone methyltransferases SET1A/SET1B. Independent study has shown that PFAP interacts with SET1B. However, unpublished studies carried out by our laboratory have suggested that PFAP interacts with SET1A. Therefore, we wished to investigate these interactions in further detail.In this study, we demonstrated that PFAP interacts with SET1A histone methyltransferase, but not SET1B. In addition, we studied localisation of SET1A to the sites of ICL repair sites. Immunofluorescence staining reveals that FLAG-tagged SET1A and RAD51 each localises to a largely non-overlapping regions of nucleus, suggesting that both FLAG-SET1A and RAD51 has distinct functions in ICL repair. Finally, we demonstrated that some Fanconi anaemia protein interacts with PFAP, thus indicating that PFAP is involved in FA pathway.

[发布机构] University:University of Birmingham;Department:Institute of Cancer Studies

[关键词] R Medicine;RC Internal medicine;RC0254 Neoplasms. Tumors. Oncology (including Cancer)