Humayun Lab
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JOBS
Postdoctoral positions
available
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Abu Amar M. Al Mamun, Ph.D.
Research Associate
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Sergey Balashov, Ph.D.
Postdoctoral Fellow
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M. Zafri Humayun, Ph. D.
Professor
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Josephine Lingutla, Ph.D.
Postdoctoral Fellow
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Fidelity of DNA Replication

        To become cancerous, a cell needs to acquire as many as 6 mutations.  Mutations occur at a canonical rate of 10-6 per gene per replication cycle. So, the probability of a cell becoming cancerous by acquiring 6 mutations is 10‑36. This calculated number is so small that theoretically no human should get cancer! Nonetheless, cancer is a common human disease, accounting for about a third of deaths in the United States.  A way to resolve this “mutation rate paradox of cancer” is to propose that mutation rates can increase well above normal levels in cells destined to become cancerous.  Cells displaying increased error levels are called mutator cells.  Mutator phenotypes can arise by the loss of a gene required to repair DNA (called permanent mutator phenotypes), or as a regulated response to changes in environmental or physiological conditions (called transient mutator phenotypes).   Transient mutator phenotypes are particularly interesting because any replicating cell can experience episodic mutation bursts, a scenario that offers a more satisfying general solution to the mutation rate paradox of cancer, as well as to other biological situations where there is a seemingly inexplicable increase in mutation rates.   Our laboratory has discovered, or co-discovered two transient mutator pathways termed UVM (for UV modulation of mutagenesis) and TSM (for translational stress-induced mutagenesis) that are currently under active investigation. 

            UVM, a pathway that is distinct from the SOS pathway, is induced when cells are subjected to DNA damaging treatments such as irradiation with UV.  UVM appears to affect translesion DNA synthesis, and appears to be mediated by an error-prone DNA polymerase whose identity has not yet been determined.   The TSM pathway, identified by us on the basis of results from other labs as well as ours is triggered, surprisingly, by increased mistranslation, and affects mutagenesis at undamaged as well as damaged DNA templates.  Expression of a variety of mutant tRNAs, as well as exposure of cells to streptomycin (an antibiotic that enhances mistranslation) can induce the TSM phenotype.   The TSM response appears to be mediated by an altered form of the major replicative DNA polymerase, namely, DNA polymerase III. We are actively investigating both pathways using a multi-disciplinary approach consisting of  classical genetics, molecular biological techniques including DNA arrays, as well as biochemical approaches requiring polymerase purification and characterization  For more info: humayun@umdnj.edu

 

 

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Job Opportunities

Postdoctoral Positions 
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Research Area: DNA replication; transient mutator pathways
Strong, interactive academic environment in a state-of-the-art research building;

excellent training opportunities
Requirements:  PhD with experience in bacterial genetics, biochemistry or molecular biology

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Send complete CV to:
 
humayun@umdnj.edu
 
M. Zafri Humayun, PhD
Professor of Microbiology and Molecular Genetics
UMDNJ-New Jersey medical School
International Center for Public Health
225 Warren Street
Newark, NJ 07101-1709
 
Lab Telephone: 973-972-4483 Ext. 25217
Office Telephone: 973-972-4483 Ext. 26396