DOI: 10.1073/pnas.0610642104. Systematic genome instability screens in yeast and their potential relevance to cancer

Systematic genome instability screens in yeast and their potential relevance to cancer

10.1073/pnas.0610642104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

To systematically identify genes that maintain genome structure, yeast knockout mutants were examined by using three assays that followed marker inheritance in different chromosomal contexts. These screens identified 130 null mutant strains exhibiting chromosome instability (CIN) phenotypes. Differences in both phenotype severity and assay specificity were observed. The results demonstrate the advantages of using complementary assays to comprehensively identify genome maintenance determinants. Genome structure was important in determining the spectrum of gene and pathway mutations causing a chromosome instability phenotype. Protein similarity identified homologues in other species, including human genes with relevance to cancer. This extensive genome instability catalog can be combined with emerging genetic interaction data from yeast to support the identification of candidate targets for therapeutic elimination of chromosomally unstable cancer cells by selective cell killing.

Bibliography

Yuen, K. W. Y., Warren, C. D., Chen, O., Kwok, T., Hieter, P., & Spencer, F. A. (2007). Systematic genome instability screens in yeast and their potential relevance to cancer. Proceedings of the National Academy of Sciences, 104(10), 3925â3930.

Authors 6

Karen W. Y. Yuen (first)
Cheryl D. Warren (additional)
Ou Chen (additional)
Teresa Kwok (additional)
Phil Hieter (additional)
Forrest A. Spencer (additional)

References 58 Referenced 138

10.1038/32688
10.1038/nrc1165
10.1073/pnas.97.1.303
10.1016/S0065-230X(03)87293-7
10.1016/S0092-8674(00)81148-4
10.1038/35053094
10.1126/science.285.5426.418
10.1038/nature02313
10.1038/ng0803-353
10.1038/nm1087
10.1038/ng1449
IM Shih, W Zhou, SN Goodman, C Lengauer, KW Kinzler, B Vogelstein Cancer Res 61, 818–822 (2001). / Cancer Res by Shih IM (2001)
10.1038/ng1409
10.1038/35101065
10.1093/genetics/106.3.365
10.1002/yea.320040404
MA Hoyt, T Stearns, D Botstein Mol Cell Biol 10, 223–234 (1990). / Mol Cell Biol by Hoyt MA (1990)
10.1093/genetics/124.2.237
10.1016/0092-8674(86)90484-8
10.1093/nar/27.15.3001
10.1073/pnas.2035018100
10.1073/pnas.0403093101
10.1126/science.285.5429.901
10.1038/nature00935
10.1126/science.1065810
10.1016/0092-8674(85)90152-7
10.1002/j.1460-2075.1990.tb07884.x
10.1128/mcb.8.6.2523-2535.1988
10.1091/mbc.e02-04-0203
10.1016/0076-6879(87)55024-8
10.1016/0076-6879(91)94057-J
10.1093/genetics/88.4.651
10.1016/0022-2836(81)90488-5
10.1128/mr.52.4.536-553.1988
10.1093/genetics/120.4.857
10.1093/nar/gkh036
10.1091/mbc.e05-09-0884
10.1534/genetics.106.057836
10.1038/sj.emboj.7600684
10.1128/MCB.25.11.4476-4487.2005
10.1093/nar/gki246
10.1091/mbc.e03-09-0637
10.1016/j.cell.2004.12.039
10.1038/12687
10.1073/pnas.2135385100
10.1016/0168-9525(90)90190-H
10.1126/science.287.5461.2204
10.1038/ng0497-339
10.1158/0008-5472.CAN-04-0587
10.1016/j.ceb.2005.09.012
10.1126/science.278.5340.1064
10.1038/nrc1691
10.1126/science.1091317
10.1016/j.cell.2005.12.036
10.1016/j.tig.2005.11.003
10.1093/nar/gkj109
10.1091/mbc.e03-08-0619
10.1038/nrc1299

Dates

Type	When
Created	18 years, 5 months ago (March 1, 2007, 6:29 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 3:11 p.m.)
Indexed	1 month ago (July 26, 2025, 4:04 a.m.)
Issued	18 years, 5 months ago (March 6, 2007)
Published	18 years, 5 months ago (March 6, 2007)
Published Online	18 years, 5 months ago (March 6, 2007)
Published Print	18 years, 5 months ago (March 6, 2007)

Funders 0

None

BibTeX

@article{Yuen_2007, title={Systematic genome instability screens in yeast and their potential relevance to cancer}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0610642104}, DOI={10.1073/pnas.0610642104}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yuen, Karen W. Y. and Warren, Cheryl D. and Chen, Ou and Kwok, Teresa and Hieter, Phil and Spencer, Forrest A.}, year={2007}, month=mar, pages={3925–3930} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        26
      ]
    ],
    "date-time": "2025-07-26T08:04:40Z",
    "timestamp": 1753517080135
  },
  "reference-count": 58,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "10",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2007,
        3,
        6
      ]
    ]
  },
  "abstract": "<jats:p>To systematically identify genes that maintain genome structure, yeast knockout mutants were examined by using three assays that followed marker inheritance in different chromosomal contexts. These screens identified 130 null mutant strains exhibiting chromosome instability (CIN) phenotypes. Differences in both phenotype severity and assay specificity were observed. The results demonstrate the advantages of using complementary assays to comprehensively identify genome maintenance determinants. Genome structure was important in determining the spectrum of gene and pathway mutations causing a chromosome instability phenotype. Protein similarity identified homologues in other species, including human genes with relevance to cancer. This extensive genome instability catalog can be combined with emerging genetic interaction data from yeast to support the identification of candidate targets for therapeutic elimination of chromosomally unstable cancer cells by selective cell killing.</jats:p>",
  "DOI": "10.1073/pnas.0610642104",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2007,
        3,
        1
      ]
    ],
    "date-time": "2007-03-01T11:29:21Z",
    "timestamp": 1172748561000
  },
  "page": "3925-3930",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 138,
  "title": "Systematic genome instability screens in yeast and their potential relevance to cancer",
  "prefix": "10.1073",
  "volume": "104",
  "author": [
    {
      "given": "Karen W. Y.",
      "family": "Yuen",
      "sequence": "first",
      "affiliation": [
        {
          "name": "*Michael Smith Laboratories,"
        },
        {
          "name": "Department of Medical Genetics, 301-2185 East Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z4; and"
        }
      ]
    },
    {
      "given": "Cheryl D.",
      "family": "Warren",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "McKusick\u2013Nathans Institute of Genetic Medicine and"
        }
      ]
    },
    {
      "given": "Ou",
      "family": "Chen",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "McKusick\u2013Nathans Institute of Genetic Medicine and"
        }
      ]
    },
    {
      "given": "Teresa",
      "family": "Kwok",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*Michael Smith Laboratories,"
        },
        {
          "name": "Department of Medical Genetics, 301-2185 East Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z4; and"
        }
      ]
    },
    {
      "given": "Phil",
      "family": "Hieter",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "*Michael Smith Laboratories,"
        },
        {
          "name": "Department of Medical Genetics, 301-2185 East Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z4; and"
        }
      ]
    },
    {
      "given": "Forrest A.",
      "family": "Spencer",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "McKusick\u2013Nathans Institute of Genetic Medicine and"
        },
        {
          "name": "Departments of \u00b6Medicine and"
        },
        {
          "name": "Molecular Biology and Genetics, 733 North Broadway, BRB447, Johns Hopkins University School of Medicine, Baltimore, MD 21205"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2007,
        3,
        6
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_4_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/32688"
    },
    {
      "key": "e_1_3_4_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrc1165"
    },
    {
      "key": "e_1_3_4_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.97.1.303"
    },
    {
      "key": "e_1_3_4_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0065-230X(03)87293-7"
    },
    {
      "key": "e_1_3_4_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0092-8674(00)81148-4"
    },
    {
      "key": "e_1_3_4_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35053094"
    },
    {
      "key": "e_1_3_4_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.285.5426.418"
    },
    {
      "key": "e_1_3_4_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature02313"
    },
    {
      "key": "e_1_3_4_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0803-353"
    },
    {
      "key": "e_1_3_4_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm1087"
    },
    {
      "key": "e_1_3_4_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng1449"
    },
    {
      "key": "e_1_3_4_12_2",
      "first-page": "818",
      "volume": "61",
      "author": "Shih IM",
      "year": "2001",
      "unstructured": "IM Shih, W Zhou, SN Goodman, C Lengauer, KW Kinzler, B Vogelstein Cancer Res 61, 818\u2013822 (2001).",
      "journal-title": "Cancer Res"
    },
    {
      "key": "e_1_3_4_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng1409"
    },
    {
      "key": "e_1_3_4_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35101065"
    },
    {
      "key": "e_1_3_4_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/106.3.365"
    },
    {
      "key": "e_1_3_4_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/yea.320040404"
    },
    {
      "key": "e_1_3_4_17_2",
      "first-page": "223",
      "volume": "10",
      "author": "Hoyt MA",
      "year": "1990",
      "unstructured": "MA Hoyt, T Stearns, D Botstein Mol Cell Biol 10, 223\u2013234 (1990).",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "e_1_3_4_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/124.2.237"
    },
    {
      "key": "e_1_3_4_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(86)90484-8"
    },
    {
      "key": "e_1_3_4_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/27.15.3001"
    },
    {
      "key": "e_1_3_4_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.2035018100"
    },
    {
      "key": "e_1_3_4_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.0403093101"
    },
    {
      "key": "e_1_3_4_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.285.5429.901"
    },
    {
      "key": "e_1_3_4_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nature00935"
    },
    {
      "key": "e_1_3_4_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1065810"
    },
    {
      "key": "e_1_3_4_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(85)90152-7"
    },
    {
      "key": "e_1_3_4_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1990.tb07884.x"
    },
    {
      "key": "e_1_3_4_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.8.6.2523-2535.1988"
    },
    {
      "key": "e_1_3_4_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e02-04-0203"
    },
    {
      "key": "e_1_3_4_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0076-6879(87)55024-8"
    },
    {
      "key": "e_1_3_4_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0076-6879(91)94057-J"
    },
    {
      "key": "e_1_3_4_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/88.4.651"
    },
    {
      "key": "e_1_3_4_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(81)90488-5"
    },
    {
      "key": "e_1_3_4_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mr.52.4.536-553.1988"
    },
    {
      "key": "e_1_3_4_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/120.4.857"
    },
    {
      "key": "e_1_3_4_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/gkh036"
    },
    {
      "key": "e_1_3_4_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e05-09-0884"
    },
    {
      "key": "e_1_3_4_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1534/genetics.106.057836"
    },
    {
      "key": "e_1_3_4_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.emboj.7600684"
    },
    {
      "key": "e_1_3_4_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.25.11.4476-4487.2005"
    },
    {
      "key": "e_1_3_4_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/gki246"
    },
    {
      "key": "e_1_3_4_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e03-09-0637"
    },
    {
      "key": "e_1_3_4_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2004.12.039"
    },
    {
      "key": "e_1_3_4_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/12687"
    },
    {
      "key": "e_1_3_4_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.2135385100"
    },
    {
      "key": "e_1_3_4_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0168-9525(90)90190-H"
    },
    {
      "key": "e_1_3_4_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.287.5461.2204"
    },
    {
      "key": "e_1_3_4_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ng0497-339"
    },
    {
      "key": "e_1_3_4_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1158/0008-5472.CAN-04-0587"
    },
    {
      "key": "e_1_3_4_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.ceb.2005.09.012"
    },
    {
      "key": "e_1_3_4_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.278.5340.1064"
    },
    {
      "key": "e_1_3_4_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrc1691"
    },
    {
      "key": "e_1_3_4_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1091317"
    },
    {
      "key": "e_1_3_4_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.cell.2005.12.036"
    },
    {
      "key": "e_1_3_4_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.tig.2005.11.003"
    },
    {
      "key": "e_1_3_4_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/gkj109"
    },
    {
      "key": "e_1_3_4_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.e03-08-0619"
    },
    {
      "key": "e_1_3_4_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nrc1299"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.0610642104",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T19:11:25Z",
    "timestamp": 1649790685000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.0610642104"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2007,
        3,
        6
      ]
    ]
  },
  "references-count": 58,
  "journal-issue": {
    "issue": "10",
    "published-print": {
      "date-parts": [
        [
          2007,
          3,
          6
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.0610642104"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.0610642104",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2007,
        3,
        6
      ]
    ]
  },
  "assertion": [
    {
      "value": "2006-05-22",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2007-03-06",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}