The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways

Alexandra Sobeck, Stacie Stone, Igor Landais, Bendert de Graaf, Maureen Hoatlin

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Genomic stability requires a functional Fanconi anemia (FA) pathway composed of an upstream "core complex" (FA proteins A/B/C/E/F/ G/L/M) that mediates monoubiquitination of the downstream targets FANCD2 and FANCI. Unique among FA core complex members, FANCM has processing activities toward replication-associated DNA structures, suggesting a vital role for FANCM during replication. Using Xenopus egg extracts, we analyzed the functions of FANCM in replication and the DNA damage response. xFANCM binds chromatin in a replication-dependent manner and is phosphorylated in response to DNA damage structures. Chromatin binding and DNA damage-induced phosphorylation of xFANCM are mediated in part by the downstream FA pathway protein FANCD2. Moreover, phosphorylation and chromatin recruitment of FANCM is regulated by two mayor players in the DNA damage response: the cell cycle checkpoint kinases ATR and ATM. Our results indicate that functions of FANCM are controlled by FA-and non-FA pathways in the DNA damage response.

Original languageEnglish (US)
Pages (from-to)25560-25568
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number38
DOIs
StatePublished - Sep 18 2009

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Fanconi Anemia Complementation Group Proteins
Automatic teller machines
DNA Damage
Fanconi Anemia
DNA
Chromatin
Phosphorylation
Fanconi Anemia Complementation Group D2 Protein
Genomic Instability
Staphylococcal Protein A
Xenopus
Cell Cycle Checkpoints
DNA Replication
Ovum
Anemia
Phosphotransferases
Cells
Processing

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways. / Sobeck, Alexandra; Stone, Stacie; Landais, Igor; de Graaf, Bendert; Hoatlin, Maureen.

In: Journal of Biological Chemistry, Vol. 284, No. 38, 18.09.2009, p. 25560-25568.

Research output: Contribution to journalArticle

Sobeck, Alexandra ; Stone, Stacie ; Landais, Igor ; de Graaf, Bendert ; Hoatlin, Maureen. / The Fanconi anemia protein FANCM is controlled by FANCD2 and the ATR/ATM pathways. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 38. pp. 25560-25568.
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