Pyrimidine dimers block simian virus 40 replication forks

Journal Article · Wed Oct 01 04:00:00 EDT 1986 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.6.10.3443· OSTI ID:7084175

Berger, C A; Edenberg, H J

UV light produces lesions, predominantly pyrimidine dimers, which inhibit DNA replication in mammalian cells. The mechanism of inhibition is controversial: is synthesis of a daughter strand halted at a lesion while the replication fork moves on and reinitiates downstream, or is fork progression itself blocked for some time at the site of a lesion. We directly addressed this question by using electron microscopy to examine the distances of replication forks from the origin in unirradiated and UV-irradiated simian virus 40 chromosomes. If UV lesions block replication fork progression, the forks should be asymmetrically located in a large fraction of the irradiated molecules; if replication forks move rapidly past lesions, the forks should be symmetrically located. A large fraction of the simian virus 40 replication forks in irradiated molecules were asymmetrically located, demonstrating that UV lesions present at the frequency of pyrimidine dimers block replication forks. As a mechanism for this fork blockage, we propose that polymerization of the leading strand makes a significant contribution to the energetics of fork movement, so any lesion in the template for the leading strand which blocks polymerization should also block fork movement.

• Research Organization: Indiana Univ. School of Medicine, Indianapolis
• OSTI ID: 7084175
• Journal Information: Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 10; ISSN MCEBD
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL RADIATION EFFECTS
CHROMOSOMES
DNA REPLICATION
ELECTROMAGNETIC RADIATION
ELECTRON MICROSCOPY
FUNCTIONS
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
INHIBITION
MICROORGANISMS
MICROSCOPY
NUCLEIC ACID REPLICATION
PARASITES
PYRIMIDINE DIMERS
RADIATION EFFECTS
RADIATIONS
SIMIAN VIRUS
ULTRAVIOLET RADIATION
VIRUSES