Yanbin Zhang, Ph.D.
Assistant Professor of Biochemistry and Molecular Biology
Description of Research
Dr. Zhang’s research interests are to unveil the molecular mechanisms of two replication-coupled DNA repair pathways, interstrand cross-link repair (ICLR) 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, 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 therapeutic 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. His 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. His study relies on the in vitro reconstituted system with defined ICL substrates and purified proteins as well as many other molecular biology tools.
Mismatch Repair: MMR corrects mismatches generated during DNA replication and escaped proofreading. Deficient MMR is the direct cause of a cancer 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. Dr. Zhang’s laboratory is interested in the biochemistry of this important repair pathway. More specifically, they employ budding yeast, Saccharomyces cerevisiae, as the eukaryotic model organism to study the mechanism of MMR and to discover novel components such as DNA nucleases and helicases. His research will be extended to human cells in order to confirm specific functions and relevance to human health of a target.
- Demonstrated that MUS81-EME1 DNA endonuclease is regulated by Fanconi anemia complementation group A protein in a damage-dependent manner.
- Revealed that Fanconi anemia complementation group A protein has intrinsic affinity to nucleic acids with preference to single-stranded forms.
- Demonstrated that FANCI interacts with FANCD2 for recognition of branched DNA structures.
Selected Cancer-Related Publications
- Shigechi T, Tomida J, Sato K, Kobayashi M, Eykelenboom JK, Pessina F, Zhang Y, Uchida E, Ishiai M, Lowndes NF, Yamamoto K, Kurumizaka H, Maehara Y, Takata M. ATR-ATRIP Kinase Complex Triggers Activation of the Fanconi Anemia DNA Repair Pathway. Cancer Res 72:1149-1156,2012 Read more »
- Yuan F, Song L, Liu F, Gu L, Zhang Y. Eukaryotic DNA mismatch repair in vitro. Methods Mol Biol 920:149-62,2012 Read more »
Collaborating in the Multidisciplinary Research Program(s):