Guang Zhu
The Hong Kong University of Science and Technology, Hong Kong
Title: Structure-functional study of G-rich oligonucleotides
Biography
Biography: Guang Zhu
Abstract
Oligonucleotides play many functional roles in cells. G-rich DNA and RNA sequences can form stable four-stranded structures termed G-quadruplexes, in which four guanine bases associate through Hoogsteen hydrogen bonding to form a square planar structure or guanine tetrad (G4). G4 motifs are evolutionarily conserved in certain regions and associated with a specific subset of the genome. Two or more guanine tetrads stack to form a G-quadruplex, which may differ in how the DNA strand(s) are folded. G4 DNA are found in telomeric sequences such as d(GGTTAG)n, and in the promoter regions of many other genes. Genome-wide search identify 370,000 potential quadruplex sequences in the human genome. It was suggested that G-quadruplex formation in a promoter may block transcription of the gene. It has also shown that RNAs also form G-quadruplex and play an important role in transcription and translation processes. We are interested in structure-functional study of G-quadruplex of DNA and RNA in human DNA replication initiation and related diseases. Our biochemical and structural study showed that human Cdc6 binds G4 DNA directly supporting a role for G4 DNA in the recruitment of Pre-RC to replication origins. In analyzing the structure of G4 DNA that Cdc6 binds, we revealed a novel structural fold of G-quadruplex of human telomeric DNA. We also investigated the role of G-rich RNA in latent DNA replication of Epstein-Barr virus. These mechanistic studies will provide insight on the molecular mechanism for origin selection in human and human viruses.