Human TopBP1 localization to the mitotic centrosome mediates mitotic progression

Sung Woong Bang, Min Ji Ko, Sukhyun Kang, Gwang Su Kim, Dongmin Kang, JooHun Lee, Deog Su Hwang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

TopBP1 contains repeats of the BRCA1 C-terminal (BRCT) domain and plays important roles in DNA damage response, DNA replication, and other cellular regulatory functions during the interphase. In prometaphase, metaphase, and anaphase, TopBP1 localizes to the mitotic centrosomes, which function as spindle-poles for the bipolar separation of sister chromatids. The localization of TopBP1 to the mitotic centrosomes is mediated by amino acid residues 1259 to 1420 in the TopBP1 C-terminal region (TbpCtr). GST and DsRed2 tags fused to TbpCtr were localized in the mitotic centrosomes, thereby suggesting that TbpCtr functions as a mitosis-specific centrosome localization signal (CLS). Mutations of Ser 1273 and/or Lys 1317, which were predicted to interact with a putative phosphoprotein, inhibited CLS function. Ectopic expression of TbpCtr specifically eliminated endogenous TopBP1 from the mitotic centrosomes, whereas mutant TbpCtr derivatives, containing substitutions at Ser 1273 and/or Lys 1317, did not. The specific elimination of TopBP1 from the mitotic centrosomes prolonged the durations of prometaphase and metaphase and shortened the inter-kinetochore distances of metaphase sister chromatids while maintaining the spindle assembly checkpoint. These results suggest that the localization of TopBP1 to the mitotic centrosomes is necessary for proper mitotic progression.

Original languageEnglish
Pages (from-to)994-1004
Number of pages11
JournalExperimental Cell Research
Volume317
Issue number7
DOIs
Publication statusPublished - 2011 Jan 1

Fingerprint

Centrosome
Metaphase
Prometaphase
Chromatids
Spindle Poles
M Phase Cell Cycle Checkpoints
Kinetochores
Anaphase
Phosphoproteins
Interphase
DNA Replication
Mitosis
DNA Damage
Amino Acids
Mutation

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Bang, Sung Woong ; Ko, Min Ji ; Kang, Sukhyun ; Kim, Gwang Su ; Kang, Dongmin ; Lee, JooHun ; Hwang, Deog Su. / Human TopBP1 localization to the mitotic centrosome mediates mitotic progression. In: Experimental Cell Research. 2011 ; Vol. 317, No. 7. pp. 994-1004.
@article{ff081a90a7ca44ba87a1172f68898719,
title = "Human TopBP1 localization to the mitotic centrosome mediates mitotic progression",
abstract = "TopBP1 contains repeats of the BRCA1 C-terminal (BRCT) domain and plays important roles in DNA damage response, DNA replication, and other cellular regulatory functions during the interphase. In prometaphase, metaphase, and anaphase, TopBP1 localizes to the mitotic centrosomes, which function as spindle-poles for the bipolar separation of sister chromatids. The localization of TopBP1 to the mitotic centrosomes is mediated by amino acid residues 1259 to 1420 in the TopBP1 C-terminal region (TbpCtr). GST and DsRed2 tags fused to TbpCtr were localized in the mitotic centrosomes, thereby suggesting that TbpCtr functions as a mitosis-specific centrosome localization signal (CLS). Mutations of Ser 1273 and/or Lys 1317, which were predicted to interact with a putative phosphoprotein, inhibited CLS function. Ectopic expression of TbpCtr specifically eliminated endogenous TopBP1 from the mitotic centrosomes, whereas mutant TbpCtr derivatives, containing substitutions at Ser 1273 and/or Lys 1317, did not. The specific elimination of TopBP1 from the mitotic centrosomes prolonged the durations of prometaphase and metaphase and shortened the inter-kinetochore distances of metaphase sister chromatids while maintaining the spindle assembly checkpoint. These results suggest that the localization of TopBP1 to the mitotic centrosomes is necessary for proper mitotic progression.",
author = "Bang, {Sung Woong} and Ko, {Min Ji} and Sukhyun Kang and Kim, {Gwang Su} and Dongmin Kang and JooHun Lee and Hwang, {Deog Su}",
year = "2011",
month = "1",
day = "1",
doi = "10.1016/j.yexcr.2011.01.022",
language = "English",
volume = "317",
pages = "994--1004",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "7",

}

Human TopBP1 localization to the mitotic centrosome mediates mitotic progression. / Bang, Sung Woong; Ko, Min Ji; Kang, Sukhyun; Kim, Gwang Su; Kang, Dongmin; Lee, JooHun; Hwang, Deog Su.

In: Experimental Cell Research, Vol. 317, No. 7, 01.01.2011, p. 994-1004.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human TopBP1 localization to the mitotic centrosome mediates mitotic progression

AU - Bang, Sung Woong

AU - Ko, Min Ji

AU - Kang, Sukhyun

AU - Kim, Gwang Su

AU - Kang, Dongmin

AU - Lee, JooHun

AU - Hwang, Deog Su

PY - 2011/1/1

Y1 - 2011/1/1

N2 - TopBP1 contains repeats of the BRCA1 C-terminal (BRCT) domain and plays important roles in DNA damage response, DNA replication, and other cellular regulatory functions during the interphase. In prometaphase, metaphase, and anaphase, TopBP1 localizes to the mitotic centrosomes, which function as spindle-poles for the bipolar separation of sister chromatids. The localization of TopBP1 to the mitotic centrosomes is mediated by amino acid residues 1259 to 1420 in the TopBP1 C-terminal region (TbpCtr). GST and DsRed2 tags fused to TbpCtr were localized in the mitotic centrosomes, thereby suggesting that TbpCtr functions as a mitosis-specific centrosome localization signal (CLS). Mutations of Ser 1273 and/or Lys 1317, which were predicted to interact with a putative phosphoprotein, inhibited CLS function. Ectopic expression of TbpCtr specifically eliminated endogenous TopBP1 from the mitotic centrosomes, whereas mutant TbpCtr derivatives, containing substitutions at Ser 1273 and/or Lys 1317, did not. The specific elimination of TopBP1 from the mitotic centrosomes prolonged the durations of prometaphase and metaphase and shortened the inter-kinetochore distances of metaphase sister chromatids while maintaining the spindle assembly checkpoint. These results suggest that the localization of TopBP1 to the mitotic centrosomes is necessary for proper mitotic progression.

AB - TopBP1 contains repeats of the BRCA1 C-terminal (BRCT) domain and plays important roles in DNA damage response, DNA replication, and other cellular regulatory functions during the interphase. In prometaphase, metaphase, and anaphase, TopBP1 localizes to the mitotic centrosomes, which function as spindle-poles for the bipolar separation of sister chromatids. The localization of TopBP1 to the mitotic centrosomes is mediated by amino acid residues 1259 to 1420 in the TopBP1 C-terminal region (TbpCtr). GST and DsRed2 tags fused to TbpCtr were localized in the mitotic centrosomes, thereby suggesting that TbpCtr functions as a mitosis-specific centrosome localization signal (CLS). Mutations of Ser 1273 and/or Lys 1317, which were predicted to interact with a putative phosphoprotein, inhibited CLS function. Ectopic expression of TbpCtr specifically eliminated endogenous TopBP1 from the mitotic centrosomes, whereas mutant TbpCtr derivatives, containing substitutions at Ser 1273 and/or Lys 1317, did not. The specific elimination of TopBP1 from the mitotic centrosomes prolonged the durations of prometaphase and metaphase and shortened the inter-kinetochore distances of metaphase sister chromatids while maintaining the spindle assembly checkpoint. These results suggest that the localization of TopBP1 to the mitotic centrosomes is necessary for proper mitotic progression.

UR - http://www.scopus.com/inward/record.url?scp=79952452813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79952452813&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2011.01.022

DO - 10.1016/j.yexcr.2011.01.022

M3 - Article

VL - 317

SP - 994

EP - 1004

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 7

ER -