Alan D. D'Andrea
Department of Radiation Oncology and Pediatrics
Radiation Oncology, Mayer Bldg., Rm. 640
450 Brookline Ave.
Boston, MA 02215
Lab Members: 8 postdoctoral fellows, 2 graduate students
Our laboratory examines the molecular signaling pathways which regulate the DNA damage response in mammalian cells. Disruption of these pathways, by germline or somatic mutation, leads to genomic instability, cellular sensitivity to ionizing radiation, and defective cell cycle checkpoints and DNA repair. These pathways are often disrupted in cancer cells, accounting for the chromosome instability and increased mutation frequency in human tumors.
Our primary focus is the molecular pathogenesis of the human chromosome instability syndromes— Fanconi Anemia (FA), Ataxia Telangiectasi (AT), and Bloom’s sydrome (BS). FA is an autosomal recessive cancer susceptibility disorder characterized by developmental defects and increased cellular sensitivity to DNA crosslinking agents. Thirteen FA genes have been cloned, and the encoded FA proteins interact in a novel signaling pathway. Eight FA proteins form a nuclear protein complex required for the monoubiquitination of the D2 protein. Activated D2 is targeted to chromatin where it interacts with the BRCA1 and BRCA2 breast cancer susceptibility gene products. Our research program addresses several aspects of this novel signaling pathway including (1) the assembly, transport, and structure of the FA protein complex (2) the enzymatic monoubiquitination and deubiquitination of the D2 protein (3) the function of the chromatin-associated FA complex in cell cycle checkpoints and homologous recombination DNA repair (4) the identification of novel interacting proteins in these complexes.
Yang K, Moldovan GL, Vinciguerra P, Murai J, Takeda S, D'Andrea AD. Regulation of the Fanconi anemia pathway by a SUMO-like delivery network. Genes Dev. 2011 Sep 1;25(17):1847-58.
Moldovan GL, Dejsuphong D, Petalcorin M, Hofmann K, Takeda S, Boulton S, D&supl;Andrea AD. Inhibition of homologous recombination by the PCNA-interacting protein PARI. 2012 Molecular Cell 45: 75-86
Kim H, Yang K, Dejsuphong D, D&supl;Andrea, AD. Regulation of Rev1 by the Fanconi Anemia Core Complex. Nat Struct Mol Biol. 2012 Jan 22;19(2):164-70.
For a complete listing of publications click here.
Last Update: 8/6/2012