Section: Rotations

Nicholas Rhind, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Biochemistry and Molecular Pharmacology

Other Affiliation(s):
   Cell Biology
   Interdisciplinary Graduate Program

Potential Rotation Projects

1) Coordination of replication and recombination by the S-phase DNA damage checkpoint.

Cells slow replication in the presence of DNA damage.  In humans and fission yeast, this slowing requires the MRN recombinational repair nuclease, consisting of Mre11, Rad50 and Nbs1. This raises the possibility that the slowing of replication is caused by induced recombinational repair.  We are testing this hypothesis using a combination of genetics, to measure induction of recombination in response to DNA damage during S-phase, biochemistry, to investigate the roles and regulation MRN's DNA binding and nuclease activities, and physical techniques, to measure the effect of the checkpoint of replication fork rate and origin use.  One possible project would be to study how the nuclease activity of MRN is regulated by checkpoint activation.

2) Regulation of S-phase transcription by the replication checkpoint.

The replication checkpoint prevents mitosis until replication is complete.It also up regulates the expression of genes required to complete replication, such as enzymes involved in nucleotide synthesis and DNA polymerization.  Using micro-array analysis, we have shown that the checkpoint up regulates most of the genes normally expressed during S-phase, suggesting that the checkpoint acts through MBF, the S-phase transcription factor. We are currently investigating how the checkpoint regulates MBF.  Interestingly, the one class of genes not regulated by the checkpoint are the histones.  Somehow, a checkpoint independent mechanism monitors replication and regulates the histone so that they are only transcribed when replication is occurring.  An interesting rotation project would be to explore the mechanism of this regulation.

Office: Research 904, Lab 940D&E
Phone: 508-856-8316
E-mail: Nick.Rhind@umassmed.edu
Keywords: Checkpoints, DNA Recombination, Cell Cycle, DNA Replication, Genetics

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