HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fan, G. Articles by Steer, C. J. Search for Related Content PubMed PubMed Citation Articles by Fan, G. Articles by Steer, C. J. Social Bookmarking                      What's this?

Volume 272, Number 31, Issue of August 1, 1997 pp. 19413-19417
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

A Novel Link Between REC2, a DNA Recombinase, the Retinoblastoma Protein, and Apoptosis

(Received for publication, February 21, 1997, and in revised form, May 30, 1997)

Guangsheng Fan , Xiaoming Ma , Betsy T. Kren , Michael Rice ^§ , Eric B. Kmiec ^§ and Clifford J. Steer ^¶

From the Departments of  Medicine and ^¶ Cell Biology and Neuroanatomy, University of Minnesota Medical School, Minneapolis, Minnesota 55455 and the ^§ Department of Pharmacology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

The REC2 recombinase is essential for recombinational repair following DNA damage as well as for successful meiosis and gene targeting in the corn smut Ustilago maydis. Here we report that overexpression of REC2 induced apoptotic cell death in human HuH-7, Hep G2, and Hep 3B hepatoma cells. Apoptosis was related to recombinase activity and was significantly increased by inhibition of retinoblastoma (Rb) expression with transforming growth factor-1. REC2-induced apoptosis was associated with a significantly reduced percentage of cells in the G₁ phase of the cell cycle and a significant reduction in G₂/M only in the Rb(/) Hep 3B cells. Overexpression of REC2 resulted in increased abundance of the hyperphosphorylated form of Rb. However, by immunoprecipitation REC2 was associated primarily with hypophosphorylated Rb, suggesting that REC2 may be involved in modulating the phosphorylation state of Rb. The A and B pocket domains with the spacer amino acid sequence and the carboxyl-terminal region of Rb were required for maximal binding to REC2. Overexpression of Rb significantly inhibited REC2-induced apoptosis even in the presence of transforming growth factor-1. Taken together, these data suggest a novel interaction of Rb with the recombinase REC2 and a role for this complex in bridging DNA recombination and apoptosis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?