DOI: 10.1073/pnas.93.26.15075. The ATM homologue <i>MEC1</i> is required for phosphorylation of replication protein A in yeast

The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast

10.1073/pnas.93.26.15075

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Replication protein A (RPA) is a highly conserved single-stranded DNA-binding protein, required for cellular DNA replication, repair, and recombination. In human cells, RPA is phosphorylated during the S and G 2 phases of the cell cycle and also in response to ionizing or ultraviolet radiation. Saccharomyces cerevisiae exhibits a similar pattern of cell cycle-regulated RPA phosphorylation, and our studies indicate that the radiation-induced reactions occur in yeast as well. We have examined yeast RPA phosphorylation during the normal cell cycle and in response to environmental insult, and have demonstrated that the checkpoint gene MEC1 is required for the reaction under all conditions tested. Through examination of several checkpoint mutants, we have placed RPA phosphorylation in a novel pathway of the DNA damage response. MEC1 is similar in sequence to human ATM, the gene mutated in patients with ataxia-telangiectasia (A-T). A-T cells are deficient in multiple checkpoint pathways and are hypersensitive to killing by ionizing radiation. Because A-T cells exhibit a delay in ionizing radiation-induced RPA phosphorylation, our results indicate a functional similarity between MEC1 and ATM, and suggest that RPA phosphorylation is involved in a conserved eukaryotic DNA damage-response pathway defective in A-T.

Bibliography

Brush, G. S., Morrow, D. M., Hieter, P., & Kelly, T. J. (1996). The ATM homologue MEC1 is required for phosphorylation of replication protein A inâyeast. Proceedings of the National Academy of Sciences, 93(26), 15075â15080.

Authors 4

George S. Brush (first)
Dwight M. Morrow (additional)
Philip Hieter (additional)
Thomas J. Kelly (additional)

References 62 Referenced 139

10.1073/pnas.84.7.1834
10.1073/pnas.85.8.2523
10.1002/j.1460-2075.1988.tb02933.x
10.1016/S0021-9258(19)39170-7
10.1016/S0021-9258(19)39750-9
10.1016/S0021-9258(18)99069-1
10.1016/S0021-9258(18)53229-4
10.1002/j.1460-2075.1990.tb07404.x
10.1101/gad.5.9.1589
10.1101/gad.4.6.968
10.1002/j.1460-2075.1992.tb05277.x
10.1128/mcb.13.12.7222-7231.1993
10.1002/j.1460-2075.1994.tb06487.x
10.1073/pnas.91.26.12520
10.1126/science.7855601
10.1126/science.7855602
10.1016/0092-8674(95)90360-7
10.1073/pnas.92.8.3171
10.1016/0092-8674(95)90482-4
10.1126/science.7792600
E C Friedberg, G C Walker, W Siede DNA Repair and Mutagenesis (Am. Soc. Microbiol., Washington, DC), pp. 662–668 (1995). / DNA Repair and Mutagenesis by Friedberg E C (1995)
10.1073/pnas.77.12.7315
10.1016/0027-5107(89)90104-8
10.1038/258427a0
10.1016/0092-8674(92)90593-2
10.1016/0092-8674(93)90496-D
10.1016/0092-8674(93)90649-B
10.1038/365079a0
10.1016/0092-8674(95)90463-8
10.1002/bies.950160810
10.1002/j.1460-2075.1994.tb06290.x
10.1016/0092-8674(95)90225-2
10.1093/nar/22.15.3104
10.1101/gad.8.6.652
10.1016/0092-8674(95)90481-6
10.1128/mcb.10.12.6554-6564.1990
10.1016/0092-8674(95)90480-8
10.1093/genetics/122.1.19
10.1016/0092-8674(95)90479-4
10.1126/science.271.5247.357
10.1101/gad.10.4.395
10.1101/gad.8.20.2401
10.1016/0092-8674(95)90448-4
10.1126/science.3291120
10.1126/science.270.5241.1488
10.1126/science.2683079
10.1038/359599a0
10.1016/0092-8674(93)90427-R
10.1016/0092-8674(93)90428-S
10.1002/j.1460-2075.1994.tb06277.x
10.1242/jcs.108.9.3109
10.1016/0092-8674(93)90650-F
10.1073/pnas.92.11.4907
10.1091/mbc.7.5.703
10.1128/mcb.14.12.7884-7890.1994
10.1002/j.1460-2075.1992.tb05110.x
10.1016/S0021-9258(18)53706-6
10.1074/jbc.270.8.4152
10.1038/374566a0
10.1128/MCB.15.10.5396
10.1074/jbc.271.31.18996
10.1073/pnas.92.10.4636

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:40 p.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 6:47 a.m.)
Issued	28 years, 8 months ago (Dec. 24, 1996)
Published	28 years, 8 months ago (Dec. 24, 1996)
Published Online	28 years, 8 months ago (Dec. 24, 1996)
Published Print	28 years, 8 months ago (Dec. 24, 1996)

Funders 0

None

BibTeX

@article{Brush_1996, title={The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast}, volume={93}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.93.26.15075}, DOI={10.1073/pnas.93.26.15075}, number={26}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Brush, George S. and Morrow, Dwight M. and Hieter, Philip and Kelly, Thomas J.}, year={1996}, month=dec, pages={15075–15080} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        11
      ]
    ],
    "date-time": "2025-07-11T10:47:08Z",
    "timestamp": 1752230828758
  },
  "reference-count": 62,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "26",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1996,
        12,
        24
      ]
    ]
  },
  "abstract": "<jats:p>\n            Replication protein A (RPA) is a highly conserved single-stranded\n DNA-binding protein, required for cellular DNA replication, repair, and\n recombination. In human cells, RPA is phosphorylated during the S and\n G\n            <jats:sub>2</jats:sub>\n            phases of the cell cycle and also in response to\n ionizing or ultraviolet radiation.\n            <jats:italic>Saccharomyces\n cerevisiae</jats:italic>\n            exhibits a similar pattern of cell cycle-regulated\n RPA phosphorylation, and our studies indicate that the\n radiation-induced reactions occur in yeast as well. We have examined\n yeast RPA phosphorylation during the normal cell cycle and in response\n to environmental insult, and have demonstrated that the checkpoint gene\n            <jats:italic>MEC1</jats:italic>\n            is required for the reaction under all conditions\n tested. Through examination of several checkpoint mutants, we have\n placed RPA phosphorylation in a novel pathway of the DNA damage\n response.\n            <jats:italic>MEC1</jats:italic>\n            is similar in sequence to human ATM, the\n gene mutated in patients with ataxia-telangiectasia (A-T). A-T cells\n are deficient in multiple checkpoint pathways and are hypersensitive to\n killing by ionizing radiation. Because A-T cells exhibit a delay in\n ionizing radiation-induced RPA phosphorylation, our results indicate a\n functional similarity between\n            <jats:italic>MEC1</jats:italic>\n            and ATM, and suggest\n that RPA phosphorylation is involved in a conserved eukaryotic DNA\n damage-response pathway defective in A-T.\n          </jats:p>",
  "DOI": "10.1073/pnas.93.26.15075",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:34:16Z",
    "timestamp": 1027694056000
  },
  "page": "15075-15080",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 139,
  "title": "The ATM homologue\n            <i>MEC1</i>\n            is required for phosphorylation of replication protein A in\u2009yeast",
  "prefix": "10.1073",
  "volume": "93",
  "author": [
    {
      "given": "George\u2009S.",
      "family": "Brush",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"
        }
      ]
    },
    {
      "given": "Dwight\u2009M.",
      "family": "Morrow",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"
        }
      ]
    },
    {
      "given": "Philip",
      "family": "Hieter",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"
        }
      ]
    },
    {
      "given": "Thomas\u2009J.",
      "family": "Kelly",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Department of Molecular Biology and Genetics, The Johns Hopkins\r University School of Medicine, Baltimore, MD 21205"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        1996,
        12,
        24
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.7.1834"
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.85.8.2523"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1988.tb02933.x"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(19)39170-7"
    },
    {
      "key": "e_1_3_2_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(19)39750-9"
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)99069-1"
    },
    {
      "key": "e_1_3_2_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)53229-4"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1990.tb07404.x"
    },
    {
      "key": "e_1_3_2_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.5.9.1589"
    },
    {
      "key": "e_1_3_2_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.4.6.968"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1992.tb05277.x"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.13.12.7222-7231.1993"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1994.tb06487.x"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.91.26.12520"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7855601"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7855602"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90360-7"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.8.3171"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90482-4"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7792600"
    },
    {
      "key": "e_1_3_2_21_2",
      "first-page": "662",
      "volume-title": "DNA Repair and Mutagenesis",
      "author": "Friedberg E C",
      "year": "1995",
      "unstructured": "E C Friedberg, G C Walker, W Siede DNA Repair and Mutagenesis (Am. Soc. Microbiol., Washington, DC), pp. 662\u2013668 (1995)."
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.77.12.7315"
    },
    {
      "key": "e_1_3_2_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0027-5107(89)90104-8"
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/258427a0"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90593-2"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90496-D"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90649-B"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/365079a0"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90463-8"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/bies.950160810"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1994.tb06290.x"
    },
    {
      "key": "e_1_3_2_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90225-2"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/22.15.3104"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.8.6.652"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90481-6"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.10.12.6554-6564.1990"
    },
    {
      "key": "e_1_3_2_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90480-8"
    },
    {
      "key": "e_1_3_2_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/genetics/122.1.19"
    },
    {
      "key": "e_1_3_2_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90479-4"
    },
    {
      "key": "e_1_3_2_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.271.5247.357"
    },
    {
      "key": "e_1_3_2_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.10.4.395"
    },
    {
      "key": "e_1_3_2_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.8.20.2401"
    },
    {
      "key": "e_1_3_2_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90448-4"
    },
    {
      "key": "e_1_3_2_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.3291120"
    },
    {
      "key": "e_1_3_2_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.270.5241.1488"
    },
    {
      "key": "e_1_3_2_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2683079"
    },
    {
      "key": "e_1_3_2_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/359599a0"
    },
    {
      "key": "e_1_3_2_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90427-R"
    },
    {
      "key": "e_1_3_2_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90428-S"
    },
    {
      "key": "e_1_3_2_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1994.tb06277.x"
    },
    {
      "key": "e_1_3_2_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1242/jcs.108.9.3109"
    },
    {
      "key": "e_1_3_2_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90650-F"
    },
    {
      "key": "e_1_3_2_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.11.4907"
    },
    {
      "key": "e_1_3_2_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1091/mbc.7.5.703"
    },
    {
      "key": "e_1_3_2_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/mcb.14.12.7884-7890.1994"
    },
    {
      "key": "e_1_3_2_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1992.tb05110.x"
    },
    {
      "key": "e_1_3_2_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)53706-6"
    },
    {
      "key": "e_1_3_2_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.270.8.4152"
    },
    {
      "key": "e_1_3_2_59_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/374566a0"
    },
    {
      "key": "e_1_3_2_60_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/MCB.15.10.5396"
    },
    {
      "key": "e_1_3_2_61_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.271.31.18996"
    },
    {
      "key": "e_1_3_2_62_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.92.10.4636"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.93.26.15075",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T18:40:07Z",
    "timestamp": 1649875207000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.93.26.15075"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1996,
        12,
        24
      ]
    ]
  },
  "references-count": 62,
  "journal-issue": {
    "issue": "26",
    "published-print": {
      "date-parts": [
        [
          1996,
          12,
          24
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.93.26.15075"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.93.26.15075",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        1996,
        12,
        24
      ]
    ]
  },
  "assertion": [
    {
      "value": "1996-10-21",
      "order": 1,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "1996-12-24",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}