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

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

Research output: Contribution to journalArticle

29 Scopus citations

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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