Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system.

Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system. Research Abstract Details 

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Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system. Abstract Text:

Federica Madia,Cristina Gattazzo,Min Wei,Paola Fabrizio,William C Burhans,Martin Weinberger,Abdoulaye Galbani,Jesse R Smith,Christopher Nguyen,Selina Huey,Lucio Comai,Valter D Longo,Federica Madia,Cristina Gattazzo,Min Wei,Paola Fabrizio,William C Burhans,Martin Weinberger,Abdoulaye Galbani,Jesse R Smith,Christopher Nguyen,Selina Huey,Lucio Comai,Valter D Longo,

Werner and Bloom syndromes are human diseases characterized by premature age-related defects including elevated cancer incidence. Using a novel Saccharomyces cerevisiae model system for aging and cancer, we show that cells lacking the RecQ helicase SGS1 (WRN and BLM homologue) undergo premature age-related changes, including reduced life span under stress and calorie restriction (CR), G1 arrest defects, dedifferentiation, elevated recombination errors, and age-dependent increase in DNA mutations. Lack of SGS1 results in a 110-fold increase in gross chromosomal rearrangement frequency during aging of nondividing cells compared with that generated during the initial population expansion. This underscores the central role of aging in genomic instability. The deletion of SCH9 (homologous to AKT and S6K), but not CR, protects against the age-dependent defects in sgs1Delta by inhibiting error-prone recombination and preventing DNA damage and dedifferentiation. The conserved function of Akt/S6k homologues in lifespan regulation raises the possibility that modulation of the IGF-I-Akt-56K pathway can protect against premature aging syndromes in mammals.

Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system. Publishing Authors By Initials

F Madia,C Gattazzo,M Wei,P Fabrizio,WC Burhans,M Weinberger,A Galbani,JR Smith,C Nguyen,S Huey,L Comai,VD Longo,F Madia,C Gattazzo,M Wei,P Fabrizio,WC Burhans,M Weinberger,A Galbani,JR Smith,C Nguyen,S Huey,L Comai,VD Longo,

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Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system. Journal Published:

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

Journal: The Journal of cell biology

VOLUME: 180

Page Numbers: 67-81

Journal Abbreviation: J. Cell Biol.

ISSN: 1540-8140

DAY: 14

MONTH: Jan

YEAR: 2008

Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system. Information

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LANGUAGE: eng

NlmUniqueID: 375356

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Grant and Affiliation Information for Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system.

AFFILIATION: Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM075308

ACRONYM: GM

MEDLINETA: J Cell Biol

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