Menin associates with FANCD2, a protein involved in repair of DNA damage.
Multiple endocrine neoplasia type I (MEN1) is an inherited tumor syndrome characterized by tumors in multiple endocrine organs including the parathyroids, pancreatic islets, and the pituitary. The gene mutated in MEN1 patients, Men1, encodes a protein of 610 amino acid residues, menin, and mutations in the Men1 gene lead to the MEN1 syndrome. Although the chromosomal instability in the peripheral lymphocytes from the MEN1 patients has been reported previously, it is not clear whether menin is involved in repair of DNA damage. Here we show that menin specifically interacts with FANCD2, a protein encoded by a gene involved in DNA repair and mutated in patients with an inherited cancer-prone syndrome, Fanconi anemia. The interaction between menin and FANCD2 is enhanced by gamma-irradiation. Moreover, loss of menin expression in mouse embryonic fibroblasts leads to increased sensitivity to DNA damage. Furthermore, menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation. Together, these results suggest that menin plays a critical role in repair of DNA damage in concert with FANCD2.
Jin
Shenghao
S
Abramson Family Cancer Research Institute, Department of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6160, USA.
Mao
Hua
H
Schnepp
Robert W
RW
Sykes
Stephen M
SM
Silva
Albert C
AC
D'Andrea
Alan D
AD
Hua
Xianxin
X
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D052236:Fanconi Anemia Complementation Group D2 Protein; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D002843:Chromatin; C499905:FANCD2 protein, human; C499904:Fancd2 protein, mouse; D052236:Fanconi Anemia Complementation Group D2 Protein; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D004247:DNA