The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder

G S Stewart; R S Maser; T Stankovic; D A Bressan; M I Kaplan; N G Jaspers; A Raams; P J Byrd; J H Petrini; A M Taylor

The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder

G S Stewart, R S Maser, T Stankovic, D A Bressan, M I Kaplan, N G Jaspers, A Raams, P J Byrd, J H Petrini, A M Taylor

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

803 Citations (Scopus)

Abstract

We show that hypomorphic mutations in hMRE11, but not in ATM, are present in certain individuals with an ataxia-telangiectasia-like disorder (ATLD). The cellular features resulting from these hMRE11 mutations are similar to those seen in A-T as well as NBS and include hypersensitivity to ionizing radiation, radioresistant DNA synthesis, and abrogation of ATM-dependent events, such as the activation of Jun kinase following exposure to gamma irradiation. Although the mutant hMre11 proteins retain some ability to interact with hRad50 and Nbs1, formation of ionizing radiation-induced hMre11 and Nbs1 foci was absent in hMRE11 mutant cells. These data demonstrate that ATM and the hMre11/hRad50/Nbs1 protein complex act in the same DNA damage response pathway and link hMre11 to the complex pathology of A-T.

Original language	English
Pages (from-to)	577-87
Number of pages	11
Journal	Cell
Volume	99
Issue number	6
Publication status	Published - 10 Dec 1999

Keywords

Ataxia Telangiectasia
Cell Cycle Proteins
Cell Line
DNA Damage
DNA Mutational Analysis
DNA Repair
DNA Repair Enzymes
DNA-Binding Proteins
Fibroblasts
Gamma Rays
Humans
Mutation, Missense
Nuclear Proteins

Cite this

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title = "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder",

abstract = "We show that hypomorphic mutations in hMRE11, but not in ATM, are present in certain individuals with an ataxia-telangiectasia-like disorder (ATLD). The cellular features resulting from these hMRE11 mutations are similar to those seen in A-T as well as NBS and include hypersensitivity to ionizing radiation, radioresistant DNA synthesis, and abrogation of ATM-dependent events, such as the activation of Jun kinase following exposure to gamma irradiation. Although the mutant hMre11 proteins retain some ability to interact with hRad50 and Nbs1, formation of ionizing radiation-induced hMre11 and Nbs1 foci was absent in hMRE11 mutant cells. These data demonstrate that ATM and the hMre11/hRad50/Nbs1 protein complex act in the same DNA damage response pathway and link hMre11 to the complex pathology of A-T.",

keywords = "Ataxia Telangiectasia, Cell Cycle Proteins, Cell Line, DNA Damage, DNA Mutational Analysis, DNA Repair, DNA Repair Enzymes, DNA-Binding Proteins, Fibroblasts, Gamma Rays, Humans, Mutation, Missense, Nuclear Proteins",

author = "Stewart, {G S} and Maser, {R S} and T Stankovic and Bressan, {D A} and Kaplan, {M I} and Jaspers, {N G} and A Raams and Byrd, {P J} and Petrini, {J H} and Taylor, {A M}",

year = "1999",

month = dec,

day = "10",

language = "English",

volume = "99",

pages = "577--87",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier",

number = "6",

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TY - JOUR

T1 - The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder

AU - Stewart, G S

AU - Maser, R S

AU - Stankovic, T

AU - Bressan, D A

AU - Kaplan, M I

AU - Jaspers, N G

AU - Raams, A

AU - Byrd, P J

AU - Petrini, J H

AU - Taylor, A M

PY - 1999/12/10

Y1 - 1999/12/10

N2 - We show that hypomorphic mutations in hMRE11, but not in ATM, are present in certain individuals with an ataxia-telangiectasia-like disorder (ATLD). The cellular features resulting from these hMRE11 mutations are similar to those seen in A-T as well as NBS and include hypersensitivity to ionizing radiation, radioresistant DNA synthesis, and abrogation of ATM-dependent events, such as the activation of Jun kinase following exposure to gamma irradiation. Although the mutant hMre11 proteins retain some ability to interact with hRad50 and Nbs1, formation of ionizing radiation-induced hMre11 and Nbs1 foci was absent in hMRE11 mutant cells. These data demonstrate that ATM and the hMre11/hRad50/Nbs1 protein complex act in the same DNA damage response pathway and link hMre11 to the complex pathology of A-T.

AB - We show that hypomorphic mutations in hMRE11, but not in ATM, are present in certain individuals with an ataxia-telangiectasia-like disorder (ATLD). The cellular features resulting from these hMRE11 mutations are similar to those seen in A-T as well as NBS and include hypersensitivity to ionizing radiation, radioresistant DNA synthesis, and abrogation of ATM-dependent events, such as the activation of Jun kinase following exposure to gamma irradiation. Although the mutant hMre11 proteins retain some ability to interact with hRad50 and Nbs1, formation of ionizing radiation-induced hMre11 and Nbs1 foci was absent in hMRE11 mutant cells. These data demonstrate that ATM and the hMre11/hRad50/Nbs1 protein complex act in the same DNA damage response pathway and link hMre11 to the complex pathology of A-T.

KW - Ataxia Telangiectasia

KW - Cell Cycle Proteins

KW - Cell Line

KW - DNA Damage

KW - DNA Mutational Analysis

KW - DNA Repair

KW - DNA Repair Enzymes

KW - DNA-Binding Proteins

KW - Fibroblasts

KW - Gamma Rays

KW - Humans

KW - Mutation, Missense

KW - Nuclear Proteins

M3 - Article

C2 - 10612394

SN - 0092-8674

VL - 99

SP - 577

EP - 587

JO - Cell

JF - Cell

IS - 6

ER -

The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder

Abstract

Keywords

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