Aneuploidy Drives Genomic Instability in Yeast

被引：298

作者：

Sheltzer, Jason M. ^{[1
,2
]}

Blank, Heidi M. ^{[1
,2
]}

Pfau, Sarah J. ^{[1
,2
]}

Tange, Yoshie ^{[3
]}

George, Benson M. ^{[1
,2
]}

Humpton, Timothy J. ^{[1
,2
]}

Brito, Ilana L. ^{[4
]}

Hiraoka, Yasushi ^{[3
,5
]}

Niwa, Osami ^{[6
]}

Amon, Angelika ^{[1
,2
]}

机构：

[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[2] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[3] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan

[4] Columbia Univ, Dept Ecol Evolut & Environm Biol, New York, NY 10027 USA

[5] Natl Inst Informat & Commun Technol, Kobe Adv ICT Res Ctr, Nishi Ku, Kobe, Hyogo 6512492, Japan

[6] Rockefeller Univ, New York, NY 10065 USA

来源：

SCIENCE | 2011年 / 333卷 / 6045期

关键词：

DOUBLE-STRAND BREAKS; RECOMBINATION; CELLS; PROLIFERATION; EVOLUTION; REPAIR;

D O I：

10.1126/science.1206412

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity. To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA damage repair. Aneuploid fission yeast strains also exhibited defects in mitotic recombination. Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer.

引用

页码：1026 / 1030

页数：5

共 23 条

[1] Meiotic Chromosome Segregation in Triploid Strains of Saccharomyces cerevisiae [J].

Charles, Jordan St. ;

Hamilton, Monica L. ;

Petes, Thomas D. .

GENETICS, 2010, 186 (02) :537-U159

[2] Bleomycins: Towards better therapeutics [J].

Chen, JY ;

Stubbe, J .

NATURE REVIEWS CANCER, 2005, 5 (02) :102-112

[3] Genetic instability of cancer cells is proportional to their degree of aneuploidy [J].

Duesberg, P ;

Rausch, C ;

Rasnick, D ;

Hehlmann, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (23) :13692-13697

[4] DNA polymerase ζ introduces multiple mutations when bypassing spontaneous DNA damage in Saccharomyces cerevisiae [J].

Harfe, BD ;

Jinks-Robertson, S .

MOLECULAR CELL, 2000, 6 (06) :1491-1499

[5] Genetic instabilities in human cancers [J].

Lengauer, C ;

Kinzler, KW ;

Vogelstein, B .

NATURE, 1998, 396 (6712) :643-649

[6] Rad52 forms DMA repair and recombination centers during S phase [J].

Lisby, M ;

Rothstein, R ;

Mortensen, UH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (15) :8276-8282

[7] Does the intrinsic instability of aneuploid genomes have a causal role in cancer? [J].

Matzke, MA ;

Mette, MF ;

Kanno, T ;

Matzke, AJM .

TRENDS IN GENETICS, 2003, 19 (05) :253-256

[8] Nuclear factories for signalling and repairing DNA double strand breaks in living fission yeast [J].

Meister, P ;

Poidevin, M ;

Francesconi, S ;

Tratner, I ;

Zarzov, P ;

Baldacci, G .

NUCLEIC ACIDS RESEARCH, 2003, 31 (17) :5064-5073

[9] The spindle-assembly checkpoint in space and time [J].

Musacchio, Andrea ;

Salmon, Edward D. .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (05) :379-393

[10]

Natarajan AT, 2006, MED INTELL UNIT, P61

← 1 2 3 →