Peter M.J. Burgers, Ph.D.

Professor
Biochemistry and Molecular Biophysics

Biochemistry, Biophysics, and Structural Biology Program
Molecular Genetics and Genomics Program
Molecular Cell Biology Program

  • 314-362-3872

  • 314-362-3182

  • 314-362-7183

  • 1911 South Building

  • burgers@wustl.edu

  • http://biochem.wustl.edu/~burgersw3/

  • Cell cycle, DNA damage response, DNA replication, Checkpoints, Mutagenesis, DNA repair, yeast

  • Molecular Biology of DNA replication and damage response in yeast and human

Research Abstract:

Our laboratory is studying DNA replication and DNA damage response mechanisms in the yeast Saccharomyces cerevisiae and in human cells. Yeast is an ideal eukaryotic organism to study questions relating to control and mechanism of replication and repair, both at a genetic and at a biochemical level. Current biochemical and genetic efforts focus on the mechanism which ensure genome fidelity during DNA replication, and on DNA damage response mechanisms that result in cell cycle checkpoint activation and in mutagenesis. It is important to understand these mechanisms in yeast because defects in the highly analogous pathways in humans are known to result in damage susceptibility and cause various forms of cancer.

Specifically, we aim to understand the functions of nuclear DNA polymerases at the replication fork under normal replication conditions, and how these functions are altered during replication stress or in response to DNA damage. The plasticity of the DNA replication fork in response to altering conditions and challenges also manifests itself at the level of Okazaki fragment maturation on the lagging strand of the fork. The presence of [4Fe-4S] clusters in each of the replicative DNA polymerases gives the potential for remarkable regulatory interactions in response to the oxidative environment of the cell.

Key factors essential for fork progression are also instrumental in coupling DNA replication to the DNA damage response pathways. One of these factors is PCNA, the circular replication clamp that coordinates these pathways through its interaction with multiple replication and repair factors. In response to DNA damage, replication forks undergo remodeling. Our biochemical and genetic studies are aimed at understanding how switching is mediated from a normal replication fork to a translesion replication fork. This switch forms the basis for damage-induced mutagenesis in all eukaryotic organisms. Damage induced mutagenesis is mediated by a complex of the Rev1 protein with DNA polymerase ζ and with PCNA, hence the mutasome, and integrated biochemical-genetic studies form a major research focus in the lab.

The DNA damage checkpoint pathway enforces cell cycle arrest to allow timely repair in response to DNA damage and replication stress. We are studying which factors in the cell are responsible for recognizing damage in distinct stages of the cell cycle, and how they start the checkpoint pathway by activation of the kinase activity of either Mec1/ATR or Tel1/ATM, the initiating protein kinase in these signal transduction pathways. Our biochemical/genetic studies of Mec1 and Tel1 are closely interconnected with complementary structural studies using cryoEM.

Selected Publications:

Tannous, E.A, Yates, L.A., Zhang, X. and Burgers, P.M. Mechanism of Auto-inhibition and Activation of Mec1ATR Checkpoint Kinase. Nat Struc Mol Biol (2020), PMID: 33169019.

Buch, R.B., Cheun, Y.K., Roy, U., Schärer, O.D. and Burgers, P.M. Bypass of DNA interstrand crosslinks by a Rev1-DNA polymerase ζ complex. Nucleic Acids Res. 48, 8461-8473 (2020) PMID: 32633759.
Hailemariam,S., De Bona, P., Hohl, M., Petrini, J., Galletto, R., and Burgers, P.M. Yeast Rif2 regulates telomere length by discharging the activated ATP form of the MRX complex. J Biol Chem, 294, 18846-18852 (2019). PMID: 31640985.

Mondol, T., Stodola, J.L., Galletto, R., and Burgers, P.M.. PCNA accelerates the nucleotide incorporation rate by DNA polymerase delta. Nucleic Acids Res. 47, 1977-1986 (2019) PMID: 30605530.

Hailemariam, S., Kumar, S., and Burgers, P.M. Activation of Tel1(ATM) kinase requires Rad50 ATPase and long nucleosome-free DNA but no DNA ends. J Biol Chem 294, 10120-10130 (2019). PMID: 31073030.

Bartels, P.L., Stodola, J.L., Burgers, P.M.J., and Barton, J.K. (2017). A Redox Role for the [4Fe4S] Cluster of Yeast DNA Polymerase delta. J Am Chem Soc 139, 18339-18348 (2017) PMID 29166001.

Stodola, J.L., Burgers, P.M. Resolving individual steps of Okazaki-fragment maturation at a millisecond timescale. Nat Struct Mol Biol. 23, 402-408 (2016) PMID: 27065195.

Sparks, J.L., and Burgers, P.M. (2015) Error-free and mutagenic processing of topoisomerase 1-provoked damage at genomic ribonucleotides. EMBO J., 34, 1259-1269 PMID: 25777529.

Last Updated: 11/23/2020 12:03:07 PM

Back To Top

Follow us: