Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells

A. J. Pierce; P. Hu; M. Han; N. Ellis; M. Jasin

doi:10.1101/gad.946401

Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells

A. J. Pierce, P. Hu, M. Han, N. Ellis, M. Jasin

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

445 Scopus citations

Abstract

Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70^-/-, XRCC4^-/-, and DNA-PKcs^-/- cells, with the increase being particularly striking in Ku70^-/- cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.

Original language	English (US)
Pages (from-to)	3237-3242
Number of pages	6
Journal	Genes and Development
Volume	15
Issue number	24
DOIs	https://doi.org/10.1101/gad.946401
State	Published - Dec 15 2001
Externally published	Yes

Keywords

DNA double-strand break
DNA-PK
Gene targeting
Homologous recombination
Ku protein
Nonhomologous end-joining
Sister-chromatid exchange

ASJC Scopus subject areas

Genetics
Developmental Biology

Access to Document

10.1101/gad.946401

Cite this

@article{1bc5915fc91b4213b860024b768eccde,

title = "Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells",

abstract = "Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70-/-, XRCC4-/-, and DNA-PKcs-/- cells, with the increase being particularly striking in Ku70-/- cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.",

keywords = "DNA double-strand break, DNA-PK, Gene targeting, Homologous recombination, Ku protein, Nonhomologous end-joining, Sister-chromatid exchange",

author = "Pierce, {A. J.} and P. Hu and M. Han and N. Ellis and M. Jasin",

year = "2001",

month = dec,

day = "15",

doi = "10.1101/gad.946401",

language = "English (US)",

volume = "15",

pages = "3237--3242",

journal = "Genes and Development",

issn = "0890-9369",

publisher = "Cold Spring Harbor Laboratory Press",

number = "24",

}

TY - JOUR

T1 - Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells

AU - Pierce, A. J.

AU - Hu, P.

AU - Han, M.

AU - Ellis, N.

AU - Jasin, M.

PY - 2001/12/15

Y1 - 2001/12/15

N2 - Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70-/-, XRCC4-/-, and DNA-PKcs-/- cells, with the increase being particularly striking in Ku70-/- cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.

AB - Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70-/-, XRCC4-/-, and DNA-PKcs-/- cells, with the increase being particularly striking in Ku70-/- cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.

KW - DNA double-strand break

KW - DNA-PK

KW - Gene targeting

KW - Homologous recombination

KW - Ku protein

KW - Nonhomologous end-joining

KW - Sister-chromatid exchange

UR - http://www.scopus.com/inward/record.url?scp=0035893363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035893363&partnerID=8YFLogxK

U2 - 10.1101/gad.946401

DO - 10.1101/gad.946401

M3 - Article

C2 - 11751629

AN - SCOPUS:0035893363

SN - 0890-9369

VL - 15

SP - 3237

EP - 3242

JO - Genes and Development

JF - Genes and Development

IS - 24

ER -

Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this