Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM

Seiki Hirano, Kazuhiko Yamamoto, Masamichi Ishiai, Mitsuyoshi Yamazoe, Masayuki Seki, Nobuko Matsushita, Mioko Ohzeki, Yukiko M. Yamashita, Hiroshi Arakawa, Jean Marie Buerstedde, Takemi Enomoto, Shunichi Takeda, Larry H. Thompson, Minoru Takata

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Some of the restarting events of stalled replication forks lead to sister chromatid exchange (SCE) as a result of homologous recombination (HR) repair with crossing over. The rate of SCE is elevated by the loss of BLM helicase or by a defect in translesion synthesis (TLS). We found that spontaneous SCE levels were elevated ∼2-fold in chicken DT40 cells deficient in Fanconi anemia (FA) gene FANCC. To investigate the mechanism of the elevated SCE, we deleted FANCC in cells lacking Rad51 paralog XRCC3, TLS factor RAD18, or BLM. The increased SCE in fance cells required Xrcc3, whereas the fancc/rad18 double mutant exhibited higher SCE than either single mutant. Unexpectedly, SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM. Furthermore, MMC-induced formation of GFP-BLM nuclear foci was severely compromised in both human and chicken fancc or fancd2 cells. Our cell survival data suggest that the FA proteins serve to facilitate HR, but not global TLS, during crosslink repair.

Original languageEnglish (US)
Pages (from-to)418-427
Number of pages10
JournalEMBO Journal
Volume24
Issue number2
DOIs
StatePublished - Jan 26 2005
Externally publishedYes

Fingerprint

Sister Chromatid Exchange
Homologous Recombination
Fanconi Anemia Complementation Group Proteins
Repair
Genes
Cells
Chickens
Defects
Fanconi Anemia
Recombinational DNA Repair
Cell Survival

Keywords

  • Bloom syndrome
  • Fanconi anemia
  • Homologous recombination
  • Sister chromatid exchange
  • Translesion synthesis

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Hirano, S., Yamamoto, K., Ishiai, M., Yamazoe, M., Seki, M., Matsushita, N., ... Takata, M. (2005). Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM. EMBO Journal, 24(2), 418-427. https://doi.org/10.1038/sj.emboj.7600534

Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM. / Hirano, Seiki; Yamamoto, Kazuhiko; Ishiai, Masamichi; Yamazoe, Mitsuyoshi; Seki, Masayuki; Matsushita, Nobuko; Ohzeki, Mioko; Yamashita, Yukiko M.; Arakawa, Hiroshi; Buerstedde, Jean Marie; Enomoto, Takemi; Takeda, Shunichi; Thompson, Larry H.; Takata, Minoru.

In: EMBO Journal, Vol. 24, No. 2, 26.01.2005, p. 418-427.

Research output: Contribution to journalArticle

Hirano, S, Yamamoto, K, Ishiai, M, Yamazoe, M, Seki, M, Matsushita, N, Ohzeki, M, Yamashita, YM, Arakawa, H, Buerstedde, JM, Enomoto, T, Takeda, S, Thompson, LH & Takata, M 2005, 'Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM', EMBO Journal, vol. 24, no. 2, pp. 418-427. https://doi.org/10.1038/sj.emboj.7600534
Hirano S, Yamamoto K, Ishiai M, Yamazoe M, Seki M, Matsushita N et al. Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM. EMBO Journal. 2005 Jan 26;24(2):418-427. https://doi.org/10.1038/sj.emboj.7600534
Hirano, Seiki ; Yamamoto, Kazuhiko ; Ishiai, Masamichi ; Yamazoe, Mitsuyoshi ; Seki, Masayuki ; Matsushita, Nobuko ; Ohzeki, Mioko ; Yamashita, Yukiko M. ; Arakawa, Hiroshi ; Buerstedde, Jean Marie ; Enomoto, Takemi ; Takeda, Shunichi ; Thompson, Larry H. ; Takata, Minoru. / Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM. In: EMBO Journal. 2005 ; Vol. 24, No. 2. pp. 418-427.
@article{8d61f5d3069048b5a817b02cafcb89da,
title = "Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM",
abstract = "Some of the restarting events of stalled replication forks lead to sister chromatid exchange (SCE) as a result of homologous recombination (HR) repair with crossing over. The rate of SCE is elevated by the loss of BLM helicase or by a defect in translesion synthesis (TLS). We found that spontaneous SCE levels were elevated ∼2-fold in chicken DT40 cells deficient in Fanconi anemia (FA) gene FANCC. To investigate the mechanism of the elevated SCE, we deleted FANCC in cells lacking Rad51 paralog XRCC3, TLS factor RAD18, or BLM. The increased SCE in fance cells required Xrcc3, whereas the fancc/rad18 double mutant exhibited higher SCE than either single mutant. Unexpectedly, SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM. Furthermore, MMC-induced formation of GFP-BLM nuclear foci was severely compromised in both human and chicken fancc or fancd2 cells. Our cell survival data suggest that the FA proteins serve to facilitate HR, but not global TLS, during crosslink repair.",
keywords = "Bloom syndrome, Fanconi anemia, Homologous recombination, Sister chromatid exchange, Translesion synthesis",
author = "Seiki Hirano and Kazuhiko Yamamoto and Masamichi Ishiai and Mitsuyoshi Yamazoe and Masayuki Seki and Nobuko Matsushita and Mioko Ohzeki and Yamashita, {Yukiko M.} and Hiroshi Arakawa and Buerstedde, {Jean Marie} and Takemi Enomoto and Shunichi Takeda and Thompson, {Larry H.} and Minoru Takata",
year = "2005",
month = "1",
day = "26",
doi = "10.1038/sj.emboj.7600534",
language = "English (US)",
volume = "24",
pages = "418--427",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Functional relationships of FANCC to homologous recombination, translesion synthesis, and BLM

AU - Hirano, Seiki

AU - Yamamoto, Kazuhiko

AU - Ishiai, Masamichi

AU - Yamazoe, Mitsuyoshi

AU - Seki, Masayuki

AU - Matsushita, Nobuko

AU - Ohzeki, Mioko

AU - Yamashita, Yukiko M.

AU - Arakawa, Hiroshi

AU - Buerstedde, Jean Marie

AU - Enomoto, Takemi

AU - Takeda, Shunichi

AU - Thompson, Larry H.

AU - Takata, Minoru

PY - 2005/1/26

Y1 - 2005/1/26

N2 - Some of the restarting events of stalled replication forks lead to sister chromatid exchange (SCE) as a result of homologous recombination (HR) repair with crossing over. The rate of SCE is elevated by the loss of BLM helicase or by a defect in translesion synthesis (TLS). We found that spontaneous SCE levels were elevated ∼2-fold in chicken DT40 cells deficient in Fanconi anemia (FA) gene FANCC. To investigate the mechanism of the elevated SCE, we deleted FANCC in cells lacking Rad51 paralog XRCC3, TLS factor RAD18, or BLM. The increased SCE in fance cells required Xrcc3, whereas the fancc/rad18 double mutant exhibited higher SCE than either single mutant. Unexpectedly, SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM. Furthermore, MMC-induced formation of GFP-BLM nuclear foci was severely compromised in both human and chicken fancc or fancd2 cells. Our cell survival data suggest that the FA proteins serve to facilitate HR, but not global TLS, during crosslink repair.

AB - Some of the restarting events of stalled replication forks lead to sister chromatid exchange (SCE) as a result of homologous recombination (HR) repair with crossing over. The rate of SCE is elevated by the loss of BLM helicase or by a defect in translesion synthesis (TLS). We found that spontaneous SCE levels were elevated ∼2-fold in chicken DT40 cells deficient in Fanconi anemia (FA) gene FANCC. To investigate the mechanism of the elevated SCE, we deleted FANCC in cells lacking Rad51 paralog XRCC3, TLS factor RAD18, or BLM. The increased SCE in fance cells required Xrcc3, whereas the fancc/rad18 double mutant exhibited higher SCE than either single mutant. Unexpectedly, SCE in the fancc/blm mutant was similar to that in blm cells, indicating functional linkage between FANCC and BLM. Furthermore, MMC-induced formation of GFP-BLM nuclear foci was severely compromised in both human and chicken fancc or fancd2 cells. Our cell survival data suggest that the FA proteins serve to facilitate HR, but not global TLS, during crosslink repair.

KW - Bloom syndrome

KW - Fanconi anemia

KW - Homologous recombination

KW - Sister chromatid exchange

KW - Translesion synthesis

UR - http://www.scopus.com/inward/record.url?scp=13444270410&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13444270410&partnerID=8YFLogxK

U2 - 10.1038/sj.emboj.7600534

DO - 10.1038/sj.emboj.7600534

M3 - Article

VL - 24

SP - 418

EP - 427

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 2

ER -