The overall aim of this proposal is to understand the mechanism(s) of gene amplification and chromosome rearrangements as studied with methotrexate resistance and the dihydrofolate reductase gene. We believe these processes involve two steps: 1) overreplication of DNA, 2) recombination to generate amplified genes as well as a wide variety of chromosomal aberrations- rearrangements.
Our specific aims i nclude: A: To define the molecular events that occur during the time that DNA replication is inhibited, which upon resumption result in overreplication of DNA. B: To determine the temporal relationship between transcription and replication of the dihydrofolate reductase gene. C: To determine if actively transcribed genes are more prone to amplification and constitute """"""""hot spots"""""""" for recombination events. D: To determine if the time of replication of a gene (or DNA sequence) is related to its propensity for amplification.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM014931-23
Application #
3268704
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1976-09-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
23
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305