Structural Biology of Mammalian Chromatin High Mobility Group Protein HMGA1 and UV-Damaged DNA
EMSL Project ID
3335
Abstract
Chromatin high mobility group protein I (HMGA1) belongs to a family of nonhistone mammalian proteins that are thought to be important structural components affecting the conformation and function of chromatin. These proteins are also known as architectural transcription factors because of their ability to function as both components of chromatin structure and as auxiliary gene transcription factors. Over-expression of HMGA1 has been observed in different types of human cancers and it has been demonstrated that such over-expression inhibits the transcription of genes coding for several proteins involved in DNA repair including DNA ligase III, Dnase X, ATM, and DNA methyltransferase. Thus, HMGA1 is also an oncoprotein (Reeves, 2000). These protein binds DNA, preferentially to the narrow minor groove of A?T rich segments. Studies suggest that it is the structure of the A?T rich DNA that HMGA1 recognizes rather than the sequence. Such DNA is a potential target site for the major type of UV damage, cyclobutane pyrimidine dimers (CPD), lesions that bend and unwind DNA (Figure 1). Consequently, there are a number of scenarios as to how MGA1 and CPD lesions interact in the nucleus. HMGA1 binding to A?T rich DNA may protect it from UV damage. HMGA1 may recognize CPD lesions in A?T rich DNA and either facilitate, or prevent, DNA repair. Conversely, CPD lesions may act to prevent the binding of HMGA1 to A?T rich DNA or displace them from the region once formed. To date, the experimental evidence does not exclusively favor any one of these scenarios and experiments are in progress in our laboratory to better establish which of these scenarios is most likely.
Project Details
Project type
Capability Research
Start Date
2003-04-12
End Date
2004-04-26
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members