FANCM: A landing pad for the Fanconi Anemia and Bloom's Syndrome complexes

Abstract

In this issue of Molecular Cell, Deans and West (2009) reveal the molecular basis of the phenotypic similarities between Fanconi Anemia (FA) and Bloom's Syndrome, identifying FANCM as the anchor for both FA and Bloom's complexes at the site of the DNA interstrand crosslink.

Fig 1. FANCM recruits both the FA core complex and BS complex at DNA crosslink sites and may explain the shared phenotypes of FA and BS patients

A) This model shows FANCM binding to the FA core complex via FANCF (via the MM1 motif) and to the BS complex via RMI1 and TopoIIIα via the MM2 motif). These interactions are believed to occur at stalled replication forks, due to DNA interstrand crosslinks. In the background of the figure some of the most common phenotypes associated with Fanconi anemia and/or Bloom's syndrome are indicated. B) In this panel, the common cellular phenotypes for Fanconi pathway deficient cells (loss of FANCD2 foci and MMC sensitivity) and BLM deficient cells (loss of BLM foci and SCEs formation) are summarized. These phenotypes were investigated in detail by Deans and West (2009) for FANCM wild type (WT) or mutants and the results are reported here. “+” indicates formation of foci and MMC sensitivity or SCEs formation. “-” indicates absence or reduction of foci and MMC resistance or absence of SCEs. The red “+” highlights interesting and unexpected new findings made in this work that further describe the interplay between FA and BS.