Seminar
Learning to Recognize Damaged DNA
Dr. Daniel BarskyBiology and Biotechnology Research Program
University of California
Lawrence Livermore National Laboratory
Monday, April 26, 1999
3:00 pm
3269 Beckman Institute
Damage to a cell's DNA can give rise to cell death or misfunction, including cancer, and thus all cellular life-forms require the capacity to repair DNA damage. Out of the ten billion bases which make up the DNA in each human cell, ten thousand bases are lost per cell per day, both spontaneously and through enzymatic removal of damaged and mismatched bases. Somehow these one-in-a-million missing bases are detected and spliced out by specific proteins known as apurinic/apyrimidinic endonucleases---Ape.
We want to know how these proteins recognize each ``abasic'' site of damage. Recent biochemical studies in our lab have ruled out previous notions of how the recognition occurs. Together these experiments and our molecular modeling of abasic DNA are suggesting that abasic DNA is recognized by its ability to attain a unique conformation upon binding to Ape.
In presenting this data, I will also reveal some surprising features of abasic DNA, and results from simulations of DNA with other forms of damage, such as interstrand crosslinks and even backbone modifications which dramatically change the helical stability of DNA. By investigating the structural and dynamical features of damaged DNA, we are pursuing the recognition mechanisms of repair proteins.
