Menin stimulates homology-directed DNA repair.
Menin, the nuclear protein encoded by the Multiple Endocrine Neoplasia type 1 (MEN1) gene, acts as a tumor suppressor. It interacts with a large number of proteins involved in chromatin modification, transcription, cell cycle checkpoint and DNA repair, though its exact function is not clear. We report that in human cells menin stimulates homology-directed (HD) DNA repair induced by the rare endonuclease I-SceI and it accumulates with Chk1 at the site of the double strand break. In addition, menin and Chk1 interact in vivo. Deletion of the first 228 amino acids of menin impairs the interaction with Chk1 and the ability to stimulate HD repair, suggesting that the complex menin-Chk1 on the damaged chromatin facilitates homologous recombination.
Istituto di Endocrinologia ed Oncologia Sperimentale-Consiglio Nazionale delle Ricerche and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università Federico II, 80131 Napoli, Italy. agallo@unina.it
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D000071877:Checkpoint Kinase 1; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D017384:Sequence Deletion
C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1