Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization

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Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization. / Jeffers, L J; Coull, B J; Stack, S J et al.
In: Oncogene, Vol. 27, No. 1, 03.01.2008, p. 139-144.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Jeffers, LJ, Coull, BJ, Stack, SJ & Morrison, CG 2008, 'Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization', Oncogene, vol. 27, no. 1, pp. 139-144. https://doi.org/10.1038/sj.onc.1210595

APA

Jeffers, L. J., Coull, B. J., Stack, S. J., & Morrison, C. G. (2008). Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization. Oncogene, 27(1), 139-144. https://doi.org/10.1038/sj.onc.1210595

Vancouver

Jeffers LJ, Coull BJ, Stack SJ, Morrison CG. Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization. Oncogene. 2008 Jan 3;27(1):139-144. doi: 10.1038/sj.onc.1210595

Author

Jeffers, L J ; Coull, B J ; Stack, S J et al. / Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization. In: Oncogene. 2008 ; Vol. 27, No. 1. pp. 139-144.

Bibtex

@article{563fa147de8843d19800a628240d3663,

title = "Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization",

abstract = "Microcephalin (MCPH1/BRIT1) forms ionizing radiation-induced nuclear foci (IRIF) and is required for DNA damage-responsive S and G(2)-M-phase checkpoints. MCPH1 contains three BRCT domains. Here we report the cloning of chicken Mcph1 (cMcph1) and functional analysis of its individual BRCT domains. Full-length cMcph1 localized to centrosomes throughout the cell cycle and formed IRIF that colocalized with gamma-H2AX. The tandem C-terminal BRCT2 and BRCT3 domains of cMcph1 were necessary for IRIF formation, while the N-terminal BRCT1 was required for centrosomal localization in irradiated cells. Centrosomal targeting of cMcph1 was independent of ATM, Brca1 or Chk1. cMcph1 formed IRIF in ATM- and Brca1-deficient cells, but not in H2AX-deficient cells. Inability to form cMcph1 IRIF impaired the cellular response to DNA damage. These results suggest that the role of microcephalin in the vertebrate DNA damage response is controlled by interaction of the C-terminal BRCT domains with gamma-H2AX.",

keywords = "Amino Acid Sequence, Animals, Avian Proteins/genetics, B-Lymphocytes/metabolism, BRCA1 Protein/genetics, Cell Line, Centrosome/metabolism, Chickens, Molecular Sequence Data, Nerve Tissue Proteins/genetics, Peptide Fragments/genetics, Protein Structure, Tertiary/genetics",

author = "Jeffers, {L J} and Coull, {B J} and Stack, {S J} and Morrison, {C G}",

year = "2008",

month = jan,

day = "3",

doi = "10.1038/sj.onc.1210595",

language = "English",

volume = "27",

pages = "139--144",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "1",

}

RIS

TY - JOUR

T1 - Distinct BRCT domains in Mcph1/Brit1 mediate ionizing radiation-induced focus formation and centrosomal localization

AU - Jeffers, L J

AU - Coull, B J

AU - Stack, S J

AU - Morrison, C G

PY - 2008/1/3

Y1 - 2008/1/3

N2 - Microcephalin (MCPH1/BRIT1) forms ionizing radiation-induced nuclear foci (IRIF) and is required for DNA damage-responsive S and G(2)-M-phase checkpoints. MCPH1 contains three BRCT domains. Here we report the cloning of chicken Mcph1 (cMcph1) and functional analysis of its individual BRCT domains. Full-length cMcph1 localized to centrosomes throughout the cell cycle and formed IRIF that colocalized with gamma-H2AX. The tandem C-terminal BRCT2 and BRCT3 domains of cMcph1 were necessary for IRIF formation, while the N-terminal BRCT1 was required for centrosomal localization in irradiated cells. Centrosomal targeting of cMcph1 was independent of ATM, Brca1 or Chk1. cMcph1 formed IRIF in ATM- and Brca1-deficient cells, but not in H2AX-deficient cells. Inability to form cMcph1 IRIF impaired the cellular response to DNA damage. These results suggest that the role of microcephalin in the vertebrate DNA damage response is controlled by interaction of the C-terminal BRCT domains with gamma-H2AX.

AB - Microcephalin (MCPH1/BRIT1) forms ionizing radiation-induced nuclear foci (IRIF) and is required for DNA damage-responsive S and G(2)-M-phase checkpoints. MCPH1 contains three BRCT domains. Here we report the cloning of chicken Mcph1 (cMcph1) and functional analysis of its individual BRCT domains. Full-length cMcph1 localized to centrosomes throughout the cell cycle and formed IRIF that colocalized with gamma-H2AX. The tandem C-terminal BRCT2 and BRCT3 domains of cMcph1 were necessary for IRIF formation, while the N-terminal BRCT1 was required for centrosomal localization in irradiated cells. Centrosomal targeting of cMcph1 was independent of ATM, Brca1 or Chk1. cMcph1 formed IRIF in ATM- and Brca1-deficient cells, but not in H2AX-deficient cells. Inability to form cMcph1 IRIF impaired the cellular response to DNA damage. These results suggest that the role of microcephalin in the vertebrate DNA damage response is controlled by interaction of the C-terminal BRCT domains with gamma-H2AX.

KW - Amino Acid Sequence

KW - Animals

KW - Avian Proteins/genetics

KW - B-Lymphocytes/metabolism

KW - BRCA1 Protein/genetics

KW - Cell Line

KW - Centrosome/metabolism

KW - Chickens

KW - Molecular Sequence Data

KW - Nerve Tissue Proteins/genetics

KW - Peptide Fragments/genetics

KW - Protein Structure, Tertiary/genetics

U2 - 10.1038/sj.onc.1210595

DO - 10.1038/sj.onc.1210595

M3 - Journal article

C2 - 17599047

VL - 27

SP - 139

EP - 144

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 1

ER -

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