Department of Biochemistry
& Molecular Biology

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     Ahmad, F.
    Briegel, K.
    Carothers-Carraway, C.
    Deutscher, M.
    Farooq, A.
    Fenna, R.
    Fletcher, T.
    Gong, F.
    Harris, TK
    Huijing, F.
    Jain, C.
    Landgraf, R.
    Malhotra, A.
    Myers, R.
    Nawaz, Z.
    Rudd, K.
    Scott, W.
    Werner, R.
    Whelan, W.
    Zhang, Y.

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DNA Core Lab

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 Yanbin Zhang

 

Assistant Professor of Biochemistry
and Molecular Biology

 

Ph.D.  (1998) Peking University, China.

 

DNA Repair, Mismatch Repair, Interstrand Cross-link Repair

Tel: (305) 243-9237

 

yzhang4@med.miami.edu

 

Research Interests:

 To deal with various genomic stresses, cells developed facinating DNA repair pathways including direct reversal, base excision repair,
global genomic nucleotide excision repair, transcription-coupled repair, double strand break repair, interstrand cross-link repair, mismatch repair, and translesion synthesis. These repair pathways safeguard genome from almost all unfavorable DNA modifications that initiate cancers. Our laboratory is interested in two repair mechanisms: interstrand cross-link (ICL) repair and mismatch repair (MMR).

 Interstrand Cross-Link Repair. ICLs are among the most toxic DNA lesions, since they covalently tether both duplex DNA strands and prevent essential DNA metabolic functions such as replication and transcription. Deficient ICL repair underlies the chromosomal instability and the hypersensitivity to DNA cross-linking agents in the cancer-prone syndromes such as Fanconi anemia, hereditary breast and ovarian cancers, and xeroderma pigmentosum. Yet, induction of ICLs is a proven strategy for the treatment of cancers and hyperproliferative disorders. It appears that ICLs represent the primary cytotoxic lesion induced by most bifunctional alkylating agents. Many clinically important cancer chemotherapeutic agents (MMC, cisplatin, psoralen, nitrogen mustard, nitrosourea and etc) are bifunctional alkylating reagents that react with both strands of the DNA helix, produce ICLs, block replication and transcription, and induce apoptosis in tumor cells. Cells can acquire resistance to such agents by repairing or tolerating these ICLs thereby compromising the therapeautic efficacy of treatment. Therefore, understanding how cells repair and tolerate ICLs will greatly facilitate the development of strategies to combat the cancer-prone diseases and to prevent drug resistance. Our laboratory is interested in decoding the mechanism of ICL repair and the specific functions of Fanconi anemia proteins, nucleotide excision repair proteins, translesion synthesis proteins, homologous recombination proteins, and ubiquitination proteins in this most complicated repair pathway. Our study relies on the in vitro reconstituted system with a defined ICL substrate and purified proteins.

Mismatch Repair (MMR). MMR corrects mismatches generated during DNA replication and escaped proofreading. Deficient MMR is the direct cause of a cander syndrome call Lynch Syndrome or hereditary nonpolyposis colorectal cancer (HNPCC). MMR is also involved in DNA damage response, mitotic and meiotic recombination, class-switch recombination, somatic hypermutation, and triplet expansion. Our laboratory is interested in the biochemistry of this important repair pathway. More specifically, we employ budding yeast, Saccharomyces cerevisiae, as the eukaryotic model organism to study the mechanism of MMR and to discover novel components such as nucleases. Our research will be extended to human cells in order to confirm specific functions and relevance to human health of a target.
Representative publications:

1.   

Zhang, Y., Yuan, F., Wang, D., Gu, L., Li, G-M. (2008) Identification of RFX as a novel mismatch repair stimulatory factor. J Biol Chem. 283, 12730-12735.

Guo, S., Zhang, Y., Yuan, F., Gao, Y., Gu, L., Wong, I., and Li, G.-M. (2006) Regulation of replication protein A functions in DNA mismatch repair by phosphorylation. J. Biol. Chem., 281, 21607-21616.

Xie, Z., Zhang, Y., Guliaev, A. B., Shen, H., Hang, B., Singer, B., and Wang, Z. (2005) The p-benzoquinone DNA adducts derived from benzene are highly mutagenic. DNA Repair, 4, 1399-1409.

Zhang, Y., Yuan, F., Presnell, S. R., Tian, K., Gao, Y., Tomkinson, A. E., Gu, L., and Li, G. -M. (2005). Reconstitution of 5’-directed human mismatch repair in a purified system. Cell, 122, 693-705. (cover story)

Guo, S., Presnell, S. R., Yuan, F., Zhang, Y., Gu, L., and Li, G. -M. (2004). Differential PCNA requirement in 5’ and 3’ nick-directed excision in human mismatch repair. J. Biol. Chem., 279, 16912-16917.

Zhang, Y., Wu, X., Guo, D., Rechkoblit, O., Taylor, J. -S., Geacintov, N. E., and Wang, Z. (2002). Lesion bypass activities of human DNA polymerase mu. J. Biol. Chem., 277, 44582-44587.

Rechkoblit, O., Zhang, Y., Guo, D., Wang, Z., Amin, S., Krzeminsky, J., Louneva, N., and Geacintov, N. E. (2002). Translesion synthesis past bulky benzo[a]pyrene diol epoxide N2-dG and N6-dA lesions catalyzed by DNA bypass polymerases. J. Biol. Chem., 277, 30488-30494.

Zhang, Y., Wu, X., Guo, D., Rechkoblit, O., and Wang, Z. (2002). Activities of human DNA polymerase kappa in response to the major benzo[a]pyrene DNA adduct: error-free lesion bypass and extension synthesis from opposite the lesion. DNA Repair, 1, 559-569.

Zhang, Y., Wu, X., Rechkoblit, O., Geacintov, N. E., Taylor, J. -S., and Wang, Z. (2002). Response of human REV1 to different DNA damage: preferential dCMP insertion opposite the lesion. Nucleic Acids Res., 30, 1630-1638.

Zhang, Y., Wu, X., Yuan, F., Xie, Z., and Wang, Z. (2001). Highly frequent frameshift DNA synthesis by human DNA polymerase mu. Mol. Cell. Biol., 21, 7995-8006.

Zhang, Y., Yuan, F., Wu, X., Taylor, J. -S., and Wang, Z. (2001). Response of human DNA polymerase iota to DNA lesions. Nucleic Acids Res., 29, 928-935.

Zhang, Y., Yuan, F., Wu, X., Rechkoblit, O., Taylor, J. -S., Geacintov, N. E., and Wang, Z. (2000). Error-prone lesion bypass by human DNA polymerase eta. Nucleic Acids Res., 28, 4717-4724.

Zhang, Y., Yuan, F., Xin, H., Wu, X., Rajpal, D. K., Yang, D., and Wang, Z. (2000). Human DNA polymerase kappa synthesizes DNA with extraordinarily low fidelity. Nucleic Acids Res., 28, 4147-4156.

Zhang, Y., Yuan, F., Wu, X., Wang, M., Rechkoblit, O., Taylor, J. -S., Geacintov, N. E., and Wang, Z. (2000). Error-free and error-prone lesion bypass by human DNA polymerase kappa in vitro. Nucleic Acids Res., 28, 4138-4146.

Zhang, Y., Yuan, F., Wu, X., and Wang, Z. (2000). Preferential incorporation of G opposite template T by the low fidelity human DNA polymerase iota. Mol. Cell. Biol., 20, 7099-7108.

Yuan, F., Zhang, Y., Rajpal, D. K., Wu, X., Guo, D., Wang, M., Taylor, J. -S., and Wang, Z. (2000). Specificity of DNA lesion bypass by the yeast DNA polymerase eta. J. Biol. Chem., 275, 8233-8239.

Honors and Professional Activities

Guest Editor, Methods

American Society for Biochemistry & Molecular Biology

American Society of Microbiology

Society of Toxicology