We study how DNA repair pathways are regulated to maintain genomic integrity

Efficient repair of DNA damage is essential for cellular survival. When cells face DNA damage from internal or external factors, multiple steps must be taken to ensure effective repair of damage as well as restoration of wild type growth.

Our lab is broadly interested in studying the regulation of DNA damage response and repair pathways in vivo.

At present, we are addressing the following questions in microbial systems:

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      a. Regulation of DNA damage response and repair clearance in bacteria

              How do cells recover after DNA damage onslaught

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      b. Regulation of pathway choice during repair

             Regulation and specificity of error-prone DNA polymerases

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      c. Molecular mechanism of double-strand break repair via homologous recombination

             How do double-strand break ends find their homologous partner

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      d. Mitochondrial DNA repair mechanisms

             How do cells regulate mitochondrial DNA damage response and repair

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We use a combination of live-cell imaging, super-resolution microscopy, high-throughput sequencing techniques as well as genetic and molecular biology assays to mechanistically understand how cells from all domains of life maintain genome integrity.

The LAB

 LAB Alumni 

• Chimthanawala, A., Parmar, J. J., Kumar, S., Iyer, K. S., Rao, M., & Badrinarayanan, A. (2022). SMC protein RecN drives RecA filament translocation for in vivo homology search. Proceedings of the National Academy of Sciences, 119(46), e2209304119.
   

• Joseph, A. M., Nahar, K., Daw, S., Hasan, M. M., Lo, R., Le, T., ... & Badrinarayanan, A. (2022). Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage. RSC Medicinal Chemistry.
   

• Dua, Nitish, Akshaya Seshadri, and Anjana Badrinarayanan. "DarT-mediated mtDNA damage induces dynamic reorganization and selective segregation of mitochondria." Journal of Cell Biology 221.10 (2022): e202205104.
   

• Badrinarayanan, A*, Leake, M.C. (2022). Fluorescence Recovery After Photobleaching (FRAP) to Study Dynamics of the Structural Maintenance of Chromosome (SMC) Complex in Live Escherichia coli Bacteria. In: Leake, M.C. (eds) Chromosome Architecture. Methods in Molecular Biology, vol 2476. 978-1-0716-2221-6_4.
   

• Adam SB Jalal, Ngat T Tran, Clare EM Stevenson, Afroze Chimthanawala, Anjana Badrinarayanan, David M Lawson, Tung BK Le*. (2021). A CTP-dependent gating mechanism enables ParB spreading on DNA. eLife. 10:e69676.
   
• Joseph A, Daw S, Sadhir I and Badrinarayanan A*. (2021). Coordination between nucleotide excision repair and specialized polymerase DnaE2 action enables survival in non-replicating bacteria. eLife. 10:e67552.

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• Raghunathan S, Chimthanawala A, Vecchiarelli A, Krishna S and Badrinarayanan A*. (2020). Asymmetric chromosome segregation and cell division in DNA damage-induced bacterial filaments. Mol Biol Cell. mbc-E20-08-0547

• Sharda M, Badrinarayanan A*, Seshasayee A* (2020). Evolutionary and Comparative analysis of bacterial Non-Homologous End Joining Repair. Genome Biol Evol. gbe/evaa223 

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• Joseph A and Badrinarayanan A*. (2020) Visualizing mutagenic repair: novel insights into bacterial translesion synthesis. FEMS Microbiology Reviews. 44, 572–582. 

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• Chimthanawala A., Badrinarayanan A*. (2019) "Live-Cell Fluorescence Imaging of RecN in Caulobacter crescentus Under DNA Damage". In: Badrinarayanan A. (eds) SMC Complexes. Methods in Molecular Biology, vol 2004.
   

• Raghunathan S., Badrinarayanan A*. (2019) "Tracking Bacterial Chromosome Dynamics with Microfluidics-Based Live Cell Imaging". In: Badrinarayanan A. (eds) SMC Complexes. Methods in Molecular Biology, vol 2004.
   

• Badrinarayanan A, Le T, Spille J, Cisse I and Laub M. "Global analysis of double-strand break processing reveals in vivo properties of the helicase-nuclease complex AddAB." PLoS genetics 13.5 2017. e1006783.

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• Badrinarayanan A and Leake M. Using Fluorescence Recovery After Photobleaching (FRAP) to study dynamics of the Structural Maintenance of Chromosome (SMC) complex in vivo. Methods in Molecular Biology, 2016. 1431:37-46.

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• Nolivos S, Upton A, Badrinarayanan A, Muller J, Zawadzka K, Wiktor J, GillA, Arciszewska L, Nicolas E, Sherratt D. MatP regulates the coordinated action of topoisomerase IV and MukBEF in chromosome segregation. Nature communications, 2016. 7:10466.

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• Badrinarayanan A, Le T, Laub M. Bacterial chromosome organization and segregation. Annual Review of Cell and Developmental Biology, 2015. 31: 171-99.

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• Badrinarayanan A, Le T, Laub M. Rapid pairing and subsequent resegregation of distant homologous loci enables DNA double-strand break repair in bacteria. The Journal of Cell Biology, 2015. 210:385-400.

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• Nicolas E, Uphoff S, Upton A, Henry O, Badrinarayanan A, Sherratt D. The SMC complex MukBEF recruits Topoisomerase IV to the origin of replication region in live Escherichia coli. MBio, 2014, 5(1), e1001-13.

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• Badrinarayanan A, Reyes-Lamothe R, Uphoff S, Leake M, Sherratt D. In vivo architecture and action of bacterial structural maintenance of chromosome proteins. Science, 2012, 338(6106), 528-531.

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• Badrinarayanan A, Lesterlin C, Reyes-Lamothe R, Sherratt D. The Escherichia coli SMC complex, MukBEF, shapes nucleoid organization independently of DNA replication. Journal of Bacteriology, 2012, 94(17), 4669-76.