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Education

August 2007                   Doctor of Philosophy (Biochemistry and Molecular Biology)

                                       University of North Dakota, USA

May 2002                        Master of Science (Biochemistry)

                                       University of Mumbai, India

May 2000                        Bachelor of Science (Biochemistry and Chemistry)

                                       University of Mumbai, India

Research

The current research in our laboratory is focused on understanding the mechanistic reactions of eukaryotic lagging strand DNA synthesis, and the accompanying DNA repair processes.   We have recently acquired evidence that many of the protein players in lagging strand DNA synthesis and base excision repair are post-translationally modified by lysine acetylation.  Accurate DNA replication and repair is a means by which eukaryotic cells maintain the integrity of their genomes. 

Understanding these processes is important because the errors that build up over decades in humans are a direct cause of aging and disease.  Studies of DNA replication and repair carried out so far, have focused on understanding the pathways and on identifying targets for cancer radiation, chemotherapeutic drugs, and anti-viral drugs.  Interestingly, recent cancer therapies have centered on the use of deacetylase inhibitors, which elevate levels of acetylation of nuclear DNA repair, heat shock and signaling proteins.

  However, we have virtually no understanding of how acetylation alters the enzymatic functions of these proteins, in turn, regulating DNA synthesis fidelity and repair.  Through our research, we are proposing to extend the scope of our current work beyond characterizing basic mechanistic pathways, to understanding how the proteins are fine-tuned by post-translational modifications to ensure best error-free replication and repair, altering mutagenesis rates. 

In particular, based on evidence from several laboratories including our current work, we propose protein lysine acetylation as a general method employed by cells to regulate the fidelity of DNA replication and repair.  In our laboratory, we will be combining three powerful tools; biochemistry, chromatin biology and genetics to understand this regulatory process. 

Publications & Professional Activities

  1. Dorota Piekna-Przybylska, Robert Bambara, Lata Balakrishnan (2016) "Acetylation Regulates DNA Repair Mechanisms in Human Cells" Cell Cycle. 15(11):1506-17
  2. Karoly Toth, Baoling Ying, Ann E. Tollefson, Jacqueline F. Spencer, Lata Balakrishnan, John E. Sagartz, R. Mark L. Buller, William S.M. Wold (2015) "Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters" Viruses, 23;7(3):1409-28
  3. Baoling Ying, Ann Tollefson, Jacqueline Spencer, Lata Balakrishnan, Stephen Dewhurst, Cristina Capella, R. Buller, Karoly Toth, and William Wold (2014), "Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters", Antimicrobial Agents and Chemotherapy, 58(12):7171-81
  4. Greg Ngo, Lata Balakrishnan, Marion Dubarry, Judith L. Campbell and David Lydall (2014), "Rad953BP1 and the 9-1-1 checkpoint clamp control DNA resection by Dna2-Sgs1BLM and Exo1", Nucleic Acids Research, 42(16):10516-28
  5. Les Kallestad, Emily Woods, Kendra Christensen, Amanda Gefroh, Lata Balakrishnan, Barry Milavetz (2013). "Transcription and Replication Result in Distinct Epigenetic Marks Following Repression of Early Gene Expression," Frontiers in Genetics, 4:140
  6. Athena Kantartzis, Gregory M. Williams, Lata Balakrishnan, Rick L. Roberts, Jennifer A. Surtees, Robert A. Bambara (2012). "Msh2-Msh3 Interferes with Okazaki Fragment Processing to Promote Trinucleotide Repeat Expansions," Cell Reports, 2(2); 216-22
  7. Jason W. Gloor, Lata Balakrishnan, Judith L. Campbell, Robert A. Bambara (2012). "Biochemical Analyses Indicate that Binding and Cleavage Specificities Define the Ordered Processing of Human Okazaki Fragments by Dna2 and FEN1," Nucleic Acids Research, 40(14):6774-86
  8. Barry Milavetz, Les Kallestad, Amanda Gefroh, Nicholas Adams, Emily Wood, Lata Balakrishnan (2012). "Virion Mediate Transfer of SV40 Epigenetic Information," Epigenetics, 7(6); 528-34
  9. Adam S. Miller, Lata Balakrishnan, Noah A. Buncher, Patricia L. Opresko, and Robert A. Bambara, (2012) "Telomere Proteins POT1, TRF1 and TRF2 Augment Long-Patch Base Excision Repair in Vitro", Cell Cycle," 11, 1-10
  10. Barbara Fortini, Subhash Pokharel, Piotr Polaczek, Lata Balakrishnan, Robert A. Bambara, Judith L. Campbell, (2011). "Characterization of the Endonuclease and ATP-Dependent Flap Endo/Exonuclease of Dna2," Journal of Biological Chemistry, 286(27):23763-70
  11. Lata Balakrishnan, Piotr Polaczek, Subhash Pokharel, Judith L. Campbell, Robert A. Bambara (2010). "Dna2 Exhibits an Unique Strand-End Dependent Helicase Mechanism," Journal of Biological Chemistry, 285(50):38861-8
  12. Jason W. Gloor, Lata Balakrishnan and Robert A. Bambara (2010), "Flap Endonuclease 1 Mechanism Analysis Indicates Flap Base Binding Prior to Threading," Journal of Biological Chemistry, 285(45):34922-31
  13. Ryan Henry, Lata Balakrishnan, Stefanie Ying-Lin, Judith L. Campbell, Robert A. Bambara (2010), "Components of the Secondary Pathway Stimulate the Primary Pathway of Eukaryotic Okazaki Fragment Processing," Journal of Biological Chemistry, 285(37):28496-505
  14. Lata Balakrishnan, Amanda Gefroh and Barry Milavetz (2010), "Histone Lysine 20 Mono- And Tri- Methylation Define Distinct Biological Processes in SV40 Minichromosomes," Cell Cycle, 9 (7), 1320 - 1332
  15. Lata Balakrishnan*, Jason Stewart*, Piotr Polaczek, Judith L. Campbell, Robert A. Bambara (2010), "Acetylation of Dna2 and Fen1 by p300 Promotes Long Flaps Favoring DNA Stability," Journal of Biological Chemistry, 285(7), 4398-404, * equal contributors
  16. Lata Balakrishnan and Barry Milavetz (2009), "Dual Agarose Magnetic (DAM) ChIP," BMC Research Notes, 2:250
  17. Lata Balakrishnan, Patrick Brandt, Laura-Lindsey Boltz, Aziz Sancar, Robert A. Bambara (2009), "Long Patch Base Excision Repair Proceeds via Co-Ordinated Stimulation of the Multi-Enzyme DNA Repair Complex," Journal of Biological Chemistry, 284(22), 15158-72
  18. Lata Balakrishnan and Barry Milavetz (2008), "HDAC Inhibitors Stimulate Viral Transcription by Multiple Mechanisms," Virology Journal, 2008 5:43
  19. Naima Kaabouch, Richard Schultz, Barry Milavetz, Lata Balakrishnan (2007), "An Analysis System for DNA Gel Electrophoresis Images Based on Automatic Thresholding and Enhancement," IEEE Electro/Information Technology Proceedings, ISBN:1424409411, pp. 33-38
  20. Lata Balakrishnan and Barry Milavetz (2007), "Histone Hyperacetylation in the Coding Region of Transcribing Chromatin is a Dynamic Process Directly Regulated by the Presence of RNA Polymerase II," Journal of Molecular Biology , 365 (1), 18-30
  21. Lata Balakrishnan and Barry Milavetz (2007), "Histone Hyperacetylation during SV40 transcription is Regulated by p300 and RNA Polymerase II Translocation," Journal of Molecular Biology, 371(4):1022-1037
  22. Lata Balakrishnan, Ryan Clauson, Timothy Weiland, Michelle Bianco, Barry Milavetz (2006), "Sexually transmitted HPV Type Variations resulting in high-grade cervical dysplasia in north-east north Dakota and north-west Minnesota," Virology Journal, 3:46
  23. Lata Balakrishnan and Barry Milavetz (2006), "Reorganization Of RNA Polymerase II on the SV40 Genome Occurs Coordinately with the Early to Late Translational Switch," Virology, 345(1):31-43
  24. Lata Balakrishnan and Barry Milavetz (2005), "Programmed Remodeling of Hyperacetylated Histones H4 and H3 Organization on the SV40 Genome During Lytic Infection," Virology, 334 (1):113-121 

Other

Invited Reviews

  1. Barry Milavetz and Lata Balakrishnan (2015), "Viral Epigenetics", Methods Mol Biol., 1238:569-96
  2. Lata Balakrishnan and Robert A. Bambara (2013), "Flap Endonuclease 1,", Annual Reviews in Biochemistry, 2;82:119-38 (Editor: Dr. Roger Kornberg)
  3. Lata Balakrishnan and Robert A. Bambara (2013), "Okazaki Fragment Maturation", DNA Replication 3rd Edition, Invited Book Chapter (Editor: Dr. Melvin DePamphilis)
  4. Lata Balakrishnan and Robert A. Bambara (2011), "Eukaryotic Lagging Strand DNA Replication Employs a Multi-Pathway Mechanism that Protects Genome Integrity," Journal of Biological Chemistry, 286(9):6865-70 (Editor: Dr. Robert Lehman)
  5. Lata Balakrishnan, Jason W. Gloor, Robert A. Bambara (2010), "Reconstitution of Eukaryotic Lagging Strand DNA Replication," Methods, 51 (3) 347-57 (Editor: Dr. Robert Brosh)
  6. Lata Balakrishnan and Barry Milavetz (2010), "Decoding the Histone H4 Lysine 20 Methylation Mark," Critical Reviews in Biochemistry and Molecular Biology, 45(5):440-52 (Editor: Dr. Michael M. Cox)

Invited Commentary

  1. Lata Balakrishnan and Robert A. Bambara (2011), "The Changing View of Dna2," Cell Cycle, 10(16):2620-1