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J. Biol. Chem., Vol. 280, Issue 26, 24784-24791, July 1, 2005

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Def1p Is Involved in Telomere Maintenance in Budding Yeast^*

Yong-Bin Chen, Cui-Ping Yang, Rong-Xia Li, Rong Zeng, and Jin-Qiu Zhou¶

From the Max-Planck Junior Research Group in the State Key Laboratory of Molecular Biology, Key laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China

Saccharomyces Rrm3p, a member of Pif1 5'-3' DNA helicase subfamily, helps replication forks traverse protein-DNA complexes, including the telomere. Here we have identified an Rrm3p interaction protein known to be Def1p. In def1 mutants, telomeres were 200-bp shorter than that in wild-type cells. DEF1 is also required for the stable maintenance of mitochondrial DNA, and the telomere shortening phenotype seen in def1 cells is not a secondary consequence of the mitochondrion defect. A combination of DEF1 null mutation with deletion of EST2 or EST3 resulted in an accelerated senescence phenotype, suggesting that Def1p is not involved in the telomerase recruitment pathway. In the absence of telomerase, cells escape senescence by either amplifying Y' regions or TG-telomeric repeats to generate type I or type II survivors, respectively. Only type I survivors were recovered from both def1 est2 and def1 est3 double mutant cells, further suggesting that the function of Def1p in telomere maintenance is specific. Our novel findings of the functions of Def1p in telomere and mitochondria suggested that Def1p plays multiple roles in yeast.

Received for publication, December 2, 2004 , and in revised form, March 28, 2005.

^* This work was supported by the Chinese Academy of Sciences, the Max-Planck Society, and the National Science Foundation of China. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^¶ To whom correspondence should be addressed: Max-Planck Junior Research Group in the State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Rd., Shanghai 200031, China. Tel.: 11-86-21-54921078; Fax: 11-86-21-54921076; E-mail: jqzhou{at}sibs.ac.cn.

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