Top

Affiliations

Education Profile

  • Ph.D. Chemistry, Research School of Chemistry, Australian National University, Canberra, 2002
  • M.S. Chemistry, Western Michigan University, 1998
  • B.S. Chemistry, Yarmouk University, Jordan, 1995

Research Interests

​Professor Hamdan's research interest is focused on the reconstitution, imaging and characterization of multi-protein nucleic acid binding machinaries at the single molecule level. Toward achieving this goal his lab uses an approach that combines conventional biochemical and biophysical tools with wide range of force and fluorescence single-molecule imaging techniques. The ability to observe enzymatic activities in real time at the single molecule level has profoundly changed how biochemical reactions are studied. By eliminating ensemble averaging, the distributions and fluctuations of molecular properties can be characterized, transient intermediates can be observed and identified, and catalytic mechanisms can be elucidated. Applying this multidisciplinary approach will provide a true molecular understanding of the mechanisms involved in replication, repair, and recombination. It will also extend the technique of single-molecule analysis from a few proteins to large multi-protein complexes, often containing many enzymatic activities.

Selected Publications

  • Hamdan SM, Marintcheva B, Cook T, Lee SJ, Tabor S, and Richardson CC. A unique loop in T7 DNA polymerase mediates the binding of helicase-primase, DNA binding protein, and processivity factor. Proceedings of the National Academy of Sciences of the USA. 2005, 102(14): 5096–5101. doi:10.1073/pnas.0501637102
  • Lee J-B, Hite RK, Hamdan SM, Xie XS, Richardson CC, and van Oijen AM. DNA primase acts as a molecular brake in DNA replication. Nature. 2006, 439(7076): 621–624.doi:10.1038/nature04317
  • Hamdan SM, Johnson DE, Tanner NA, Lee, J-B, Qimron U, Tabor S, van Oijen AM, and Richardson CC. Dynamic DNA helicase-DNA polymerase interactions assure processive replication fork movement. Molecular Cell. 2007, 27(4): 539–549 doi:10.1016/j.molcel.2007.06.020
  • Hamdan SM, Loparo JJ, Takahashi M, Richardson CC, and van Oijen AM. Dynamics of DNA replication loops reveal temporal control of lagging-strand synthesis. Nature. 2009, 457(7227): 336–339. doi:10.1038/nature07512
  • Hamdan SM and Richardson CC. Motors, switches, and contacts in the replisome. Annual Review of Biochemistry. 2009, 78: 205–243.doi:10.1146/annurev.biochem.78.072407.103248
  • Sobhy MA, Joudeh LI, Huang X, Takahashi M, and Hamdan SM. Sequential and multistep substrate interrogation provides the scaffold for specificity in human flap endonuclease 1.Cell Reports. 2013, 3(6): 1785–1794. doi:10.1016/j.celrep.2013.05.001
  • Iwata Y, Takahashi M, Fedoroff NV and Hamdan SM. Dissecting the interactions of SERRATE with RNA and DICER-LIKE 1 in Arabidopsis microRNA precursor processing. Nucleic Acids Research. 2013, 41(19): 9129-40. doi:10.1093/nar/gkt667
  • Elshenawy MM, Jergic S, Xu Z-Q, Sobhy MA, Takashi M, Oakley AJ, Dixon NE, and Hamdan SM. Replisome speed determines the efficiency of the Tus−Ter replication termination barrier. Nature. 2015, 525(7569): 394–398. doi:10.1038/nature14866.
  • Rashid F, Harris PD, Zaher MS, Sobhy MA, Joudeh IL, Yan C, Piwonski H, Tsutakawa SE, Ivanov I, Tainer JA, Habuchi S, and Hamdan SM. Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1. Elife. 2017, 6.pii: e21884. doi:10.7554/elife.21884
  • Takahashi M, Takahashi E, Joudeh LI, Marini M, Das G, Elshenawy MM, Akal A, Sakashita K, Tehseen M, Sobhy MA, Stingl U, Merzaban JS, Di Fabrizio E, and Hamdan SM. Dynamic structure mediates halophilic adaptation of a DNA polymerases from the deep-sea brines of the Red sea. FASEB J. 2018. doi:10.1096/fj.201700862RR
  • Zaher MS, Rashid F, Song B, Joudeh LI, Sobhy MA, Tehseen M, Hingorani MM, and Hamdan SM. Missed Cleavage opportunities by FEN1 lead to Okazaki fragments maturations via the long-flap pathway. Nucleic Acids Research. 2018. doi:10.1093/nar/gky082
  • Sobhy MA, Bralic A, Raducanu VS, Takahashi M, Teshseen M, Rashid F, Zaher MA and Hamdan SM. Resolution of the Holliday junction recombination intermediate by human GEN1 at the single-molecule level. Nucleic Acids Research. 2019. doi:10.1093/nar/gky1280.
  • Rashid F, Raducanu VS, Zaher MS, Tehseen M, Habuchi S, and Hamdan SM. Initial state of DNA-dye complex sets the stage for protein induced fluorescence modulation. Nature Communications. 2019. doi:10.1038/s41467-019-10137-9.
  • Lancey C, Tehseen M, Raducanu VS, Rashid F, Merino N, Ragan TJ, Savva C, Zaher MS, Blanco FJ, Hamdan SM# and De Biasio A#. Structure of the processive human Pol δ holoenzyme. Nature Communications. 2020. doi:10.1038/s41467-020-14898-6.