Document Detail

Regulation of DNA replication in S phase nuclei by ATP and ADP pools.
MedLine Citation:
PMID:  287004     Owner:  NLM     Status:  MEDLINE    
Synchronized 3T6 (mouse fibroblast) ghost monolayers (isolated nuclei) were utilized to study the effects of ATP and ADP levels on DNA replication in vitro. A system yielding discontinuous semiconservative DNA replication (without any detectable repair) in synchronized S phase nuclei has been developed. Lack of initiation of new sites has been observed in isolated S phase 3T6 nuclei without the presence of cytoplasmic material; DNA synthesis is comprised only of elongation at sites where initiation had previously taken place. DNA synthesis in S phase nuclei proceeded optimally at an ATP concentration of 4-5 mM. High ATP levels as well as high ATP/ADP ratios (produced by an ATP-regenerating system at a variety of ATP concentrations) yielded marked inhibition of [(3)H]dTTP incorporation. The cellular and nuclear pools of ATP and ADP in intact synchronized 3T6 cells were accurately determined by high-pressure liquid chromatography. A good correlation with the studies on isolated nuclei has been observed. Whereas total cellular ATP pools increase during the progression of 3T6 cells from G(1) to S phase of the cell cycle, nuclear ATP pools do not increase, and the nuclear ATP/ADP ratios decrease once the cells enter the S phase of their cycle. These experiments suggest that nuclear ATP pools and ATP/ADP ratios act as S phase controls, regulating DNA elongation at sites where its synthesis has previously been initiated by cytoplasmic factors.
E Rapaport; M A Garcia-Blanco; P C Zamecnik
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  76     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1979 Apr 
Date Detail:
Created Date:  1979-08-16     Completed Date:  1979-08-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1643-7     Citation Subset:  IM    
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MeSH Terms
Adenosine Diphosphate / metabolism*
Adenosine Triphosphate / metabolism*
Cell Cycle*
Cell Line
Cell Nucleus / metabolism*
DNA Replication*
Thymidine / metabolism
Reg. No./Substance:
50-89-5/Thymidine; 56-65-5/Adenosine Triphosphate; 58-64-0/Adenosine Diphosphate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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