Aneel K. Aggarwal
- PROFESSOR Structural and Chemical Biology
- PROFESSOR Oncological Sciences
Ph.D., Kings College, University of London
Protein-nucleic acid interactions: studied by X-ray crystallography and other biophysical methodsResearch 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 (Pol eta, Pol iota, Pol kappa and Rev1), which possess the ability to replicate through DNA lesions that would otherwise stall the replication machinery. Mutations in Pol eta 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 elucidated 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.
Ummat A, Rechkoblit O, Jain R, Roy Choudhury J, Johnson RE, Silverstein TD, Buku A, Lone S, Prakash L, Prakash S, Aggarwal AK. Structural basis for cisplatin DNA damage tolerance by human polymerase η during cancer chemotherapy. Nature Struct. & Mol. Biol. 2012; 19: 628-632.
Silverstein TD, Johnson RE, Jain R, Prakash L, Prakash S, Aggarwal AK. Structural basis for the suppression of skin cancers by DNA polymerase eta. Nature 2010; 465: 1039-1043.
Swan MK, Johnson RE, Prakash L, Prakash S, Aggarwal AK. Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta. Nature Struct. & Mol. Biol. 2009; 16: 979-986.
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.
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-iota occurs by Hoogsteen base-pairing. Nature 2004; 430: 377-380.
Kumar V, Carlson JE, Ohgi KA, Edwards TA, Rose DW, Escalante CR, Rosenfeld MG, Aggarwal AK. Transcription corepressor CtBP is an NAD(+)-regulated dehydrogenase. Mol. Cell 2002; 10: 1127-1131.
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.
Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM. Structure and ligand of a histone acetyltransferase bromodomain. Nature 1999; 399: 491-496.
Passner JM, Ryoo HD, Shen L, Mann RS, Aggarwal AK. Structure of a DNA-bound Ultrabithorax-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.
Wah DA, Hirsch JA, Dorner LF, Schildkraut I, Aggarwal AK. Structure of the multimodular endonuclease FokI bound to DNA. Nature 1997; 388: 97-100.
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.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Aggarwal did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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