Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing.

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing. Research Abstract Details 

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Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing. Abstract Text:

Haiyan Pan,Yan Deng,Jeffrey W Pollard,

In the uterus, progesterone (P4) acts early in G1 as a physiological inhibitor of estradiol-17beta (E2)-induced epithelial cell proliferation. Gene expression profiling of uterine epithelial cell RNA isolated 3 h after hormonal treatment of ovariectomized mice revealed the co-coordinate down-regulation by P4 of >20 genes whose functions are associated with DNA replication. This group included all of the minichromosome maintenance (MCM) proteins that are required for DNA replication licensing. E2 regulated loading of these MCM proteins onto chromatin in parallel with its induction of DNA synthesis. E2 caused this chromatin loading by retention of MCM proteins in the nucleus and through the induction of the loading factor Cdt1, which is necessary for the MCM heterohexamer to bind to the origin of DNA replication. P4 dramatically reduced the binding of the MCMs to chromatin by a number of mechanisms. First, MCM mRNA and protein abundance was down-regulated. Second, P4 inhibited the E2 induction of Cdt1. Third, P4 treatment sequestered the normally nuclear MCM proteins into the cytoplasm. This reduced MCM binding resulted in the complete inhibition of E2-induced DNA synthesis by P4. These data reveal mechanisms not only for female sex steroid hormone action but also in the regulation of DNA replication licensing.

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing. Publishing Authors By Initials

H Pan,Y Deng,JW Pollard,

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Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 14021-6

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ISSN: 0027-8424

DAY: 11

MONTH: 09

YEAR: 2006

Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Progesterone blocks estrogen-induced DNA synthesis through the inhibition of replication licensing.

AFFILIATION: Department of Development and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Country: United States

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MEDLINETA: Proc Natl Acad Sci U S A

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