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Title: Modeling DNA Replication Intermediates

While there is now available a great deal of information on double stranded DNA from X-ray crystallography, high resolution NMR and computer modeling, very little is known about structures that are representative of the DNA core of replication intermediates. DNA replication occurs at a single strand/double strand junction and bulged out intermediates near the junction can lead to frameshift mutations. The single stranded domains are particularly challenging. Our interest is focused on strategies for modeling the DNA of these types of replication intermediates. Modeling such structures presents special problems in addressing the multiple minimum problem and in treating the electrostatic component of the force field. We are testing a number of search strategies for locating low energy structures of these types and we are also investigating two different distance dependent dielectric functions in the coulombic term of the force field. We are studying both unmodified DNA and DNA damaged by aromatic amines, carcinogens present in the environment in tobacco smoke, barbecued meats and automobile exhaust. The nature of the structure adopted by the carcinogen modified DNA at the replication fork plays a key role in determining whether the carcinogen will cause a mutation during replication that can initiate the carcinogenicmore » process. In the present work results are presented for unmodified DNA.« less
Authors:
; ;
Publication Date:
OSTI Identifier:
3524
Report Number(s):
ORNL/CP-101136
TRN: AH200112%%329
DOE Contract Number:
AC05-96OR22464
Resource Type:
Conference
Resource Relation:
Conference: 10th Conversation in the Discipline Biomolecular Stereodynamics, Albany, NY (US), 06/1997; Other Information: PBD: 1 Jun 1997
Research Org:
Oak Ridge National Lab., TN (US)
Sponsoring Org:
USDOE Office of Energy Research (ER) (US)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; REACTION INTERMEDIATES; MORPHOLOGY; DNA REPLICATION; MATHEMATICAL MODELS; POLYCYCLIC AROMATIC AMINES; BIOLOGICAL EFFECTS