SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair

Vyacheslav Yurchenko, Zhu Xue, Moshe J. Sadofsky

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The nonhomologous end-joining (NHEJ) pathway is responsible for rejoining the majority of double-strand breaks in mammalian cells, including the programmed breaks introduced by V(D)J recombination. The regulation of the enzymatic activities associated with this recombination pathway is still largely unknown. Here we report that human XRCC4 (for X-ray cross-complementation group 4), a protein essential for NHEJ, is subject to posttranslational protein modification. The modifier peptide, SUMO, can be added to XRCC4 both in vitro and in vivo. The site of modification is mapped to lysine 210 by using specific mutagenesis. A protein mutated such that it cannot be SUMOylated remains localized in the cytoplasm rather than accumulating in the nucleus. Cells expressing only the mutated protein are radiation sensitive and fail to complete V(D)J recombination. Genetic fusion of the SUMO sequence to the C terminus of the mutant restores nuclear localization and radiation resistance. The modification may serve a regulatory role. Our finding fits with an emerging literature associating SUMO modification with the control of the repair and recombination associated with DNA breaks.

Original languageEnglish (US)
Pages (from-to)1786-1794
Number of pages9
JournalMolecular and Cellular Biology
Volume26
Issue number5
DOIs
StatePublished - Mar 2006

Fingerprint

Double-Stranded DNA Breaks
X-Rays
V(D)J Recombination
Proteins
Radiation
Recombinational DNA Repair
DNA Breaks
Post Translational Protein Processing
Mutagenesis
Genetic Recombination
Lysine
Cytoplasm
Peptides

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair. / Yurchenko, Vyacheslav; Xue, Zhu; Sadofsky, Moshe J.

In: Molecular and Cellular Biology, Vol. 26, No. 5, 03.2006, p. 1786-1794.

Research output: Contribution to journalArticle

@article{01fbcd54a7f44043b0fd850f28287cbb,
title = "SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair",
abstract = "The nonhomologous end-joining (NHEJ) pathway is responsible for rejoining the majority of double-strand breaks in mammalian cells, including the programmed breaks introduced by V(D)J recombination. The regulation of the enzymatic activities associated with this recombination pathway is still largely unknown. Here we report that human XRCC4 (for X-ray cross-complementation group 4), a protein essential for NHEJ, is subject to posttranslational protein modification. The modifier peptide, SUMO, can be added to XRCC4 both in vitro and in vivo. The site of modification is mapped to lysine 210 by using specific mutagenesis. A protein mutated such that it cannot be SUMOylated remains localized in the cytoplasm rather than accumulating in the nucleus. Cells expressing only the mutated protein are radiation sensitive and fail to complete V(D)J recombination. Genetic fusion of the SUMO sequence to the C terminus of the mutant restores nuclear localization and radiation resistance. The modification may serve a regulatory role. Our finding fits with an emerging literature associating SUMO modification with the control of the repair and recombination associated with DNA breaks.",
author = "Vyacheslav Yurchenko and Zhu Xue and Sadofsky, {Moshe J.}",
year = "2006",
month = "3",
doi = "10.1128/MCB.26.5.1786-1794.2006",
language = "English (US)",
volume = "26",
pages = "1786--1794",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - SUMO modification of human XRCC4 regulates its localization and function in DNA double-strand break repair

AU - Yurchenko, Vyacheslav

AU - Xue, Zhu

AU - Sadofsky, Moshe J.

PY - 2006/3

Y1 - 2006/3

N2 - The nonhomologous end-joining (NHEJ) pathway is responsible for rejoining the majority of double-strand breaks in mammalian cells, including the programmed breaks introduced by V(D)J recombination. The regulation of the enzymatic activities associated with this recombination pathway is still largely unknown. Here we report that human XRCC4 (for X-ray cross-complementation group 4), a protein essential for NHEJ, is subject to posttranslational protein modification. The modifier peptide, SUMO, can be added to XRCC4 both in vitro and in vivo. The site of modification is mapped to lysine 210 by using specific mutagenesis. A protein mutated such that it cannot be SUMOylated remains localized in the cytoplasm rather than accumulating in the nucleus. Cells expressing only the mutated protein are radiation sensitive and fail to complete V(D)J recombination. Genetic fusion of the SUMO sequence to the C terminus of the mutant restores nuclear localization and radiation resistance. The modification may serve a regulatory role. Our finding fits with an emerging literature associating SUMO modification with the control of the repair and recombination associated with DNA breaks.

AB - The nonhomologous end-joining (NHEJ) pathway is responsible for rejoining the majority of double-strand breaks in mammalian cells, including the programmed breaks introduced by V(D)J recombination. The regulation of the enzymatic activities associated with this recombination pathway is still largely unknown. Here we report that human XRCC4 (for X-ray cross-complementation group 4), a protein essential for NHEJ, is subject to posttranslational protein modification. The modifier peptide, SUMO, can be added to XRCC4 both in vitro and in vivo. The site of modification is mapped to lysine 210 by using specific mutagenesis. A protein mutated such that it cannot be SUMOylated remains localized in the cytoplasm rather than accumulating in the nucleus. Cells expressing only the mutated protein are radiation sensitive and fail to complete V(D)J recombination. Genetic fusion of the SUMO sequence to the C terminus of the mutant restores nuclear localization and radiation resistance. The modification may serve a regulatory role. Our finding fits with an emerging literature associating SUMO modification with the control of the repair and recombination associated with DNA breaks.

UR - http://www.scopus.com/inward/record.url?scp=33644540769&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644540769&partnerID=8YFLogxK

U2 - 10.1128/MCB.26.5.1786-1794.2006

DO - 10.1128/MCB.26.5.1786-1794.2006

M3 - Article

C2 - 16478998

AN - SCOPUS:33644540769

VL - 26

SP - 1786

EP - 1794

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 5

ER -