ROLES OF UBIQUITIN CONJUGATING ENZYMES IN DNA REPAIR

Project Details

Description

The yeast RAD52 epistasis group of genes are involved in DNA
recombination and repair of DNA damaged by radiation and other
environmental agents such as cross-linking and alkylating agents. While
screening for proteins that associate with human RAD52 protein using
the yeast two hybrid system, we have cloned the human homolog of yeast
ubiquitin-conjugating enzymes S. cerevisiae UBC9 or S. pombe Hus5.
Human UBC9 also associates with RAD51, tumor suppressor protein p53 and
a newly identified mitosis-related protein hRAP12. Considering these
interactions and the fact that yeast UBC9 homologs are involved in S-
and M-phase cyclin degradation, mitosis control and radiation
sensitivity, we suggest that human UBC9 participates in repairing DNA
damage induced by environmental agents, cell cycle control, and p53-
mediated processes.

The objective of this research is to understand the functions and
mechanisms of UBC9 in the context of DNA repair, cell cycle control,
and p53-mediated processes after DNA has been damaged by radiation and
other environmental stresses. The specific aims for this FIRST proposal
are: 1)to determine whether human UBC9 protein forms a stable complex
with RAD51, RAD52, p53, and hRAP12; 2)to determine whether direct
protein-protein binding is involved in these interactions; 3)to
characterize the regulation of human UBC9 expression by radiation
exposure and during the cell cycle; 4)to determine whether
increased/reduced expression of human UBC9 protein will affect cellular
resistance to radiation and cell cycle progression; 5)to identify novel
proteins that may associate with UBC9, RAD51, RAD52, and hRAP12. It is
expected that once the proposed goals are accomplished, we will gain
more insights about how environmentally induced DNA damage is repaired,
and how the repair processes are coordinated with other processes, such
as cell cycle control and p53-mediated processes.
StatusFinished
Effective start/end date12/1/9611/30/02

ASJC

  • Genetics
  • Radiation
  • Molecular Biology
  • Cell Biology

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