Gender	Male
E-mail	aneel.aggarwal@mssm.edu
Education and Training	Ph.D., Kings College

Education and Training	Ph.D., Kings College

Protein-nucleic acid interactions: studied by X-ray crystallography and other biophysical methods
Research in our laboratory represents a consistent effort to understand how enzymes, and transcriptional and translational regulators interact with nucleic acids to affect cellular development and disease outcome. Amongst the enzymes we are studying are eukaryotic translesion DNA synthesis polymerases (Poln Poll, Polk and Rev1), which have the ability to replicate through DNA lesions that would otherwise stall the replication machinery. Mutations in Poln, for example, cause of variant form of xeroderma pigmentosum (XPV), a heritable, cancer-prone syndrome in humans. We are also deeply interested in questions of specificity and how proteins translocate on DNA to select the correct sequence from the sea of nonspecific sequences in a cell.  Here, our effort is focused on restriction endonucleases such as BamHI, and, we have, for example, determined structures of BamHI at almost every stage of its catalytic pathway.  The work on transcription is motivated by questions of specificity in vivo, as they relate to homeotic proteins; and, in understanding the innate cellular response to viral infection mediated by interferon regulatory factors (IRFs).  Transcription is, however, only one mechanism for regulating gene expression. Translational regulation plays an equally important role, but an understanding of the underlying mechanisms has been hindered by the lack of structural data. As such, we are exploring the structures of several key proteins that control mRNA translation during early fly development.

Escalante CR, Nistal-Villan E, Shen L, Garcia-Sastre A, Aggarwal AK. Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer. Mol. Cell 2007; 26: 703-716.

Lone S, Townson SA, Uljon SN, Johnson RE, Brahma A, Nair DT, Prakash S, Prakash L, Aggarwal AK. Human DNA polymerase-K encircles DNA: Implications for mismatch extension and lesion bypass. Mol. Cell 2007; 25: 601-614.

Vanamee ES, Berriman J, Aggarwal AK. An EM view of the FokI synaptic complex by single particle analysis. J. Mol. Biol 2007; 370: 207-212.

Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Rev1 employs a novel mechanism of DNA synthesis using a protein template. Science 2005; 309: 2219-2222.

Nair DT, Johnson RE, Prakash S, Prakash L, Aggarwal AK. Replication by human DNA polymerase-l occurs by Hoogsteen base-pairing. Nature 2004; 430: 377-380.

Edwards TA, Pyle S, Wharton RP, Aggarwal AK. Structure of Pumilio reveals similarity in RNA and peptide binding motifs. Cell 2001; 105: 281-289.

Trincao J, Johnson RE, Escalante CR, Prakash S, Prakash L, Aggarwal AK. Structure of the catalytic core of S. cerevisiae DNA polymerase n: implication for translesion DNA synthesis. Mol. Cell 2001; 8: 439-488.

Scully K, Jacobson EM, Jepsen K, Lunyak V, Viadiu H, Carriere C, Rose DW, Hooshmand F, Aggarwal AK, Rosenfeld MG. Allosteric effects of Pit-1 DNA sites on long-term repression in cell-type specification. Science 2000; 290: 1127-1132.

Viadiu H, Aggarwal AK. Structure of BamHI bound to non-specific DNA: A model for DNA sliding. Mol. Cell 2000; 5: 889-895.

Passner JM, Ryoo HD, Shen L, Mann RS, Aggarwal AK. Structure of a DNA-boundUltrabithorax-Extradenticle homeodomain complex. Nature 1999; 397: 714-719.

Escalante CR, Yie J, Thanos D, Aggarwal AK. Structure of IRF-1 with bound DNA reveals determinants of interferon regulation. Nature 1998; 391: 103-106.

Newman M, Strzelecka T, Dorner LF, Schildkraut I, Aggarwal AK. Structure of BamHI endonuclease bound to DNA: Partial folding and unfolding on DNA binding. Science 1995; 269: 656-663.