Fanconi anemia proteins stabilize replication forks

Lily Chien Wang, Stacie Stone, Maureen Hoatlin, Jean Gautier

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Fanconi anemia (FA) is a recessive genetic disorder characterized by hypersensitivity to crosslinking agents that has been attributed to defects in DNA repair and/or replication. FANCD2 and the FA core complex bind to chromatin during DNA replication; however, the role of FA proteins during replication is unknown. Using Xenopus cell-free extracts, we show that FANCL depletion results in defective DNA replication restart following treatment with camptothecin, a drug that results in DSBs during DNA replication. This defect is more pronounced following treatment with mitomycin C, presumably because of an additional role of the FA pathway in DNA crosslink repair. Moreover, we show that chromatin binding of FA core complex proteins during DNA replication follows origin assembly and origin firing and is dependent on the binding of RPA to ssDNA while FANCD2 additionally requires ATR, consistent with FA proteins acting at replication forks. Together, our data suggest that FA proteins play a role in replication restart at collapsed replication forks.

Original languageEnglish (US)
Pages (from-to)1973-1981
Number of pages9
JournalDNA Repair
Volume7
Issue number12
DOIs
StatePublished - Dec 1 2008

Fingerprint

Fanconi Anemia Complementation Group Proteins
Fanconi Anemia
DNA Replication
DNA
DNA Repair
Chromatin
Repair
Camptothecin
Inborn Genetic Diseases
Replication Origin
Mitomycin
Defects
Xenopus
Cell Extracts
Hypersensitivity
Crosslinking
Pharmaceutical Preparations

Keywords

  • Fanconi anemia
  • Mitomycin C
  • Replication forks
  • Replication restart

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fanconi anemia proteins stabilize replication forks. / Wang, Lily Chien; Stone, Stacie; Hoatlin, Maureen; Gautier, Jean.

In: DNA Repair, Vol. 7, No. 12, 01.12.2008, p. 1973-1981.

Research output: Contribution to journalArticle

Wang, Lily Chien ; Stone, Stacie ; Hoatlin, Maureen ; Gautier, Jean. / Fanconi anemia proteins stabilize replication forks. In: DNA Repair. 2008 ; Vol. 7, No. 12. pp. 1973-1981.
@article{1ff1e659329a45ce810243f07a74bb9a,
title = "Fanconi anemia proteins stabilize replication forks",
abstract = "Fanconi anemia (FA) is a recessive genetic disorder characterized by hypersensitivity to crosslinking agents that has been attributed to defects in DNA repair and/or replication. FANCD2 and the FA core complex bind to chromatin during DNA replication; however, the role of FA proteins during replication is unknown. Using Xenopus cell-free extracts, we show that FANCL depletion results in defective DNA replication restart following treatment with camptothecin, a drug that results in DSBs during DNA replication. This defect is more pronounced following treatment with mitomycin C, presumably because of an additional role of the FA pathway in DNA crosslink repair. Moreover, we show that chromatin binding of FA core complex proteins during DNA replication follows origin assembly and origin firing and is dependent on the binding of RPA to ssDNA while FANCD2 additionally requires ATR, consistent with FA proteins acting at replication forks. Together, our data suggest that FA proteins play a role in replication restart at collapsed replication forks.",
keywords = "Fanconi anemia, Mitomycin C, Replication forks, Replication restart",
author = "Wang, {Lily Chien} and Stacie Stone and Maureen Hoatlin and Jean Gautier",
year = "2008",
month = "12",
day = "1",
doi = "10.1016/j.dnarep.2008.08.005",
language = "English (US)",
volume = "7",
pages = "1973--1981",
journal = "DNA Repair",
issn = "1568-7864",
publisher = "Elsevier",
number = "12",

}

TY - JOUR

T1 - Fanconi anemia proteins stabilize replication forks

AU - Wang, Lily Chien

AU - Stone, Stacie

AU - Hoatlin, Maureen

AU - Gautier, Jean

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Fanconi anemia (FA) is a recessive genetic disorder characterized by hypersensitivity to crosslinking agents that has been attributed to defects in DNA repair and/or replication. FANCD2 and the FA core complex bind to chromatin during DNA replication; however, the role of FA proteins during replication is unknown. Using Xenopus cell-free extracts, we show that FANCL depletion results in defective DNA replication restart following treatment with camptothecin, a drug that results in DSBs during DNA replication. This defect is more pronounced following treatment with mitomycin C, presumably because of an additional role of the FA pathway in DNA crosslink repair. Moreover, we show that chromatin binding of FA core complex proteins during DNA replication follows origin assembly and origin firing and is dependent on the binding of RPA to ssDNA while FANCD2 additionally requires ATR, consistent with FA proteins acting at replication forks. Together, our data suggest that FA proteins play a role in replication restart at collapsed replication forks.

AB - Fanconi anemia (FA) is a recessive genetic disorder characterized by hypersensitivity to crosslinking agents that has been attributed to defects in DNA repair and/or replication. FANCD2 and the FA core complex bind to chromatin during DNA replication; however, the role of FA proteins during replication is unknown. Using Xenopus cell-free extracts, we show that FANCL depletion results in defective DNA replication restart following treatment with camptothecin, a drug that results in DSBs during DNA replication. This defect is more pronounced following treatment with mitomycin C, presumably because of an additional role of the FA pathway in DNA crosslink repair. Moreover, we show that chromatin binding of FA core complex proteins during DNA replication follows origin assembly and origin firing and is dependent on the binding of RPA to ssDNA while FANCD2 additionally requires ATR, consistent with FA proteins acting at replication forks. Together, our data suggest that FA proteins play a role in replication restart at collapsed replication forks.

KW - Fanconi anemia

KW - Mitomycin C

KW - Replication forks

KW - Replication restart

UR - http://www.scopus.com/inward/record.url?scp=55149115113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55149115113&partnerID=8YFLogxK

U2 - 10.1016/j.dnarep.2008.08.005

DO - 10.1016/j.dnarep.2008.08.005

M3 - Article

C2 - 18786657

AN - SCOPUS:55149115113

VL - 7

SP - 1973

EP - 1981

JO - DNA Repair

JF - DNA Repair

SN - 1568-7864

IS - 12

ER -