Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break

Carol M Anderson; Dmitry Korkin; Dana L Smith; Svetlana Makovets; Jeffrey J Seidel; Andrej Sali; Elizabeth H Blackburn

doi:10.1101/gad.1646208

Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break

Carol M Anderson, Dmitry Korkin, Dana L Smith, Svetlana Makovets, Jeffrey J Seidel, Andrej Sali, Elizabeth H Blackburn

School of Biological Sciences

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

Abstract / Description of output

The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

Original language	English
Pages (from-to)	854-859
Number of pages	6
Journal	Genes & Development
Volume	22
Issue number	7
DOIs	https://doi.org/10.1101/gad.1646208
Publication status	Published - 2008

Keywords / Materials (for Non-textual outputs)

DNA damage signaling
checkpoint
Clk-2
PI3 kinase-like kinase
α-superhelical protein
telomere

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title = "Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break",

abstract = "The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.",

keywords = "DNA damage signaling, checkpoint, Clk-2, PI3 kinase-like kinase, α-superhelical protein, telomere",

author = "Anderson, {Carol M} and Dmitry Korkin and Smith, {Dana L} and Svetlana Makovets and Seidel, {Jeffrey J} and Andrej Sali and Blackburn, {Elizabeth H}",

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language = "English",

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T1 - Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break

AU - Anderson, Carol M

AU - Korkin, Dmitry

AU - Smith, Dana L

AU - Makovets, Svetlana

AU - Seidel, Jeffrey J

AU - Sali, Andrej

AU - Blackburn, Elizabeth H

PY - 2008

Y1 - 2008

N2 - The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

AB - The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae) control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and Tel2 interact, and that even when Tel1 protein levels are high, this interaction is specifically required for Tel1 localization to a DNA break and its activation of downstream targets. Computational analysis revealed structural homology between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a common structural principle used by partners of phoshoinositide 3-kinase-like kinases.

KW - DNA damage signaling

KW - checkpoint

KW - Clk-2

KW - PI3 kinase-like kinase

KW - α-superhelical protein

KW - telomere

U2 - 10.1101/gad.1646208

DO - 10.1101/gad.1646208

M3 - Article

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SN - 0890-9369

VL - 22

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JO - Genes & Development

JF - Genes & Development

IS - 7

ER -

Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand break

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Keywords / Materials (for Non-textual outputs)

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