Genome Integrity Group

The Genome Integrity Group (GIG) at UNC Charlotte is made up of a collaborative group of investigators involved in interdisciplinary research to understand DNA replication, recombination, damage and repair mechanisms in cancer and other human diseases. The GIG at UNC Charlotte aims to develop novel technologies and methodologies to investigate genome integrity. In addition to publishing high impact research, the GIG aims to provide an enriching training environment for Postdoctoral researchers, Graduate and Undergraduate students.

Current members include Dr. Shan Yan (Molecular mechanisms of genome integrity and cancer etiology), Dr. Christine Richardson (DNA recombination and repair and cancer biology), Dr. Andrew Truman (Role of Molecular chaperones in the DNA damage response), Dr. Kausik Chakrabarti (RNA regulation in human pathogens and telomerase), and Dr. Junya Tomida (DNA repair, kinase regulation, cancer carcinogenesis and metastasis). This group of five labs meets every month for presentations by lab members and discussions and collaborations within the GIG group.

For more about Dr. Chakrabarti's lab, visit his research lab webpage.

Research projects

  1. Structure and function of RNA and ribonucleoprotein complexes.

  2. Telomerase regulation and genome integrity in unicellular pathogens.

  3. Post-transcriptional mRNA processing in cell proliferation and cancer. 

Representative Publications

  1. Dey A, Chakrabarti K. Current Perspectives of Telomerase Structure and Function in Eukaryotes with Emerging Views on Telomerase in Human Parasites. Int J Mol Sci. 2018;19(2). Epub 2018/01/25. doi: 10.3390/ijms19020333. PMID: 29364142; 

  2. Ares M, Jr., Chakrabarti K*. Stuttering against marginotomy. Nat Struct Mol Biol. 2008;15(1):18-9. Epub 2008/01/08. doi: 10.1038/nsmb0108-18. PMID: 18176550.

  3. Sandhu R, Sanford S, Basu S, Park M, Pandya UM, Li B, Chakrabarti K*. A trans-spliced telomerase RNA dictates telomere synthesis in Trypanosoma brucei. Cell Res. 2013;23(4):537-51. Epub 2013/03/13. doi: 10.1038/cr.2013.35. PubMed PMID: 23478302; PMCID: PMC3616428.

For more about Dr. Richardson's lab, visit her research lab webpage.

Research projects

  1. DNA damage and translocations caused by bioflavonoids.

  2. DNA repair pathway choice.

  3. In vivo models of homologous recombination and non-homologous endjoining to repair double strand breaks. 

Representative Publications

  1. Goodenow D, Emmanuel F, Berman C, Sahyouni M, Richardson C. Bioflavonoids cause DNA double-strand breaks and chromosomal translocations through topoisomerase II-dependent and -independent mechanisms. Mut Res: Gen Tox Env Gen. available online 2020.

  2. Bariar BB, Vestal CV, Deem B, Goodenow D, Ughetta M, Engledove W, Sahyouni M, Richardson C. Bioflavonoids promote stable translocations between MLL-AF9 breakpoint cluster regions independent of chromosomal context: model system to screen environmental risks. Env. Mol. Mutagenesis, 2019 PMID: 30387535. 

  3. White, R, Sung, P, Vestal, CG, Benedetto, G., Cornelio, N., and Richardson, C. Double-strand break repair by interchromosomal recombination: an in vivo repair mechanism utilized by multiple somatic tissues in mammals.  PlosONE, 8(12): 1-16, 2013. e84379. PMID: 24349572 PMCID: PMC3862804

For more about Dr. Tomida's lab, visit his research lab webpage.

Research projects

  1. Define factors leading to metastasis and chemoresistance in prostate, breast, and ovarian cancers (knockout mouse and cell)

  2. Characterization of protein complex of DNA repair proteins

  3. DNA interstrand crosslink repair pathway

Representative Publications

  1. Tomida J, Takata KI, Bhetawal S, Person MD, Chao HP, Tang DG, Wood RD. FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells. EMBO J. 2018;37(12). Epub 2018/05/24. doi: 10.15252/embj.201899543. PMID: 29789392. co-corresponding author 

  2. Tomida J, Takata K, Lange SS, Schibler AC, Yousefzadeh MJ, Bhetawal S, Dent SY, Wood RD. REV7 is essential for DNA damage tolerance via two REV3L binding sites in mammalian DNA polymerase ζ. Nucleic Acids Res 43(2):1000-11, 1/2015. e-Pub 1/2015.  PMCID: PMC4333420.

  3. Tomida J, Itaya A, Shigechi T, Unno J, Uchida E, Ikura M, Masuda Y, Matsuda S, Adachi J, Kobayashi M, Meetei AR, Maehara Y, Yamamoto K, Kamiya K, Matsuura A, Matsuda T, Ikura T, Ishiai M, Takata M. A novel interplay between the Fanconi anemia core complex and ATR-ATRIP kinase during DNA cross-link repair. Nucleic Acids Res 41(14):6930-41, 8/2013. e-Pub 5/2013. PMCID: PMC3737553.

  4.  

For more about Dr. Truman's lab, visit his research lab webpage.

Research projects

  1. Regulation of the DNA damage response by molecular chaperones

  2. Understanding Hsp70 phosphorylation in cancer

  3. Using cross-linking mass spectrometry to understand PTM-driven chaperones interactions

Representative Publications

 
  1. Xu L, Nitika, Hasin N, Cuskelly DD, Wolfgeher D, Doyle S, Moynagh P, Perrett S, Jones GW, Truman AW*. Rapid deacetylation of yeast Hsp70 mediates the cellular response to heat stress. Sci Rep. 2019;9(1):16260. doi: 10.1038/s41598-019-52545-3. PubMed PMID: 31700027.

  2. Ricco N, Flor A, Wolfgeher D, Efimova EV, Ramamurthy A, Appelbe OK, Brinkman J, Truman AW, Spiotto MT, Kron SJ. Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer. Mol Oncol. 2019;13(9):1927-43. Epub 2019/06/22. doi: 10.1002/1878-0261.12535. PubMed PMID: 31225926. 

  3. Knighton LE, Delgado LE, Truman AW*. Novel insights into molecular chaperone regulation of ribonucleotide reductase. Curr Genet. 2019;65(2):477-82. Epub 2018/12/07. doi: 10.1007/s00294-018-0916-7. PubMed PMID: 30519713; 

  4. Sluder IT, Nitika, Knighton LE, Truman AW*. The Hsp70 co-chaperone Ydj1/HDJ2 regulates ribonucleotide reductase activity. PLoS Genet. 2018;14(11):e1007462. Epub 2018/11/20. doi: 10.1371/journal.pgen.1007462. PubMed PMID: 30452489.

  5. Truman AW, Kristjansdottir K, Wolfgeher D, Hasin N, Polier S, Zhang H, Perrett S, Prodromou C, Jones GW, Kron SJ. CDK-dependent Hsp70 Phosphorylation controls G1 cyclin abundance and cell-cycle progression. Cell. 2012;151(6):1308-18. Epub 2012/12/12. doi: 10.1016/j.cell.2012.10.051. PubMed PMID: 23217712.

For more about Dr. Yan's lab, visit his research lab webpage

Research projects

  1. DNA Single-strand break repair and signaling

  2. Oxidative stress response and redox regulation

  3. DNA replication stress response in genome stability

  4. DNA repair and DNA damage response pathways in human diseases (cancer, sepsis, aging, and neurodegenerative diseases)

Representative Publications

  1. Lin Y, Raj J, Li J, Ha A, Hossain MA, Richardson C, Mukherjee P, Yan S*. 2019. APE1 senses DNA single-strand breaks for repair and signaling. Nucleic Acids Research. (PMID: 31828326; Epub ahead of print) DOI: https://doi.org/10.1093/nar/gkz1175

  2. Lin Y, Bai L, Cupello S, Hossain MA, Deem B, McLeod M, Raj J, Yan S*. 2018. APE2 promotes DNA damage response pathway from a single-strand break. Nucleic Acids Research. 46 (5): 2479-2494. (PMCID: PMC5861430; PMID: 29361157)

  3. Wallace BD§, Berman Z§,, Mueller GA, Lin Y, Chang T, Andres SN, Wojtaszek JL, DeRose EF, Appel CD, London RE, Yan S*, Williams RS*. 2017.  APE2 Zf-GRF facilitates 3′-5′ resection of DNA damage following oxidative stress. Proceedings of the National Academy of Sciences of the United States of America. 114 (2):304-309. (PMCID: PMC5240719; PMID: 28028224)

  4. Yan S*, Sorrell M, Berman Z¶. 2014. Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cellular and Molecular Life Sciences. 71 (20): 3951-3967. (PMCID: PMC4176976; PMID: 24947324)

  5. Willis J§, Patel Y§, Lentz B,  Yan S*. 2013. APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proceedings of the National Academy of Sciences of the United States of America. 110 (26): 10592-10597. (PMCID: PMC3696815; PMID: 23754435).