ROLE OF C-MYC PROTEIN IN DNA REPLICATION

  • Studzinski, George (PI)

Project Details

Description

The oncogene c-myc is abnormally expressed in several forms of
human cancer, notably Burkitt's lymphoma, colorectal carcinoma
and promyelocytic leukemia. It is known that this gene is highly
expressed in these cells, due to its amplification or chromosomal
translocation, but how this results in abnormal cellular growth has
not been clear. Recent work in this laboratory indicated that c-
myc protein participates in DNA replication of human cells.
Thus, overexpression of this gene product would confer a
proliferative advantage to the cell, by making it less dependent on
external growth stimuli. It is proposed to exploit this finding to
determine more precisely the step or steps in DNA replication
which are dependent on the c-myc gene product. The DNA
replication complex will be dissociated and reconstituted
following an exposure to affinity-purified polyclonal and
monoclonal antibodies to c-myc (alpha-myc). Re-addition of
individual components of the replication machinery will identify
cellular proteins that react with alpha-myc. Studies with
replicating molecules of SV 40 virus will provide conditions
analogous to an amplified mammalian replication unit, and thus
permit a closer analysis of the stepwise maturation of nascent
DNA. The role of oncogene c-fos, in cells which express this
oncogene, in DNA replication or maintenance of chromatin
structure will be addressed by sequential immunocytochemical
and in situ hybridization studies, and related to DNA replicative
activity. These studies should provide a beginning for the
clarification of the physiological functions of oncogenes encoding
nuclear phosphoproteins.
StatusFinished
Effective start/end date9/1/8712/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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