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. 2009 Dec 24;139(7):1222-4.
doi: 10.1016/j.cell.2009.12.006.

FANCD2 hurdles the DNA interstrand crosslink

George-Lucian Moldovan  1 , Alan D D'Andrea
Affiliations

FANCD2 hurdles the DNA interstrand crosslink

George-Lucian Moldovan et al. Cell. .

Abstract

Left unrepaired, DNA interstrand crosslinks represent impassable hurdles for DNA replication, and their removal is a complicated stepwise process involving a variety of enzymes. In a recent paper in Science, Knipscheer et al. (2009) demonstrate that the Fanconi Anemia protein FANCD2 promotes multiple steps of the crosslink repair process.

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Figures

Figure 1
Figure 1. FANCD2 monoubiquitination is required for the nucleolytic incision and translesion bypass steps of interstrand crosslink repair
Crosslink repair is initiated by stalling of the two replication forks on either side of the crosslink. One of the forks subsequently moves to the crosslink site. By the time the fork reaches position -1, FANCD2 has been monoubiquitinated by the FA core complex. Ubiquitinated FANCI-FANCD2 then promotes nucleolytic incisions and crosslink unhooking, allowing bypass of the lesion by polymerases. Finally, homologous recombination concludes the repair reaction. Monoubiquitinated FANCD2 may directly activate nucleolytic processes (A), recruit translesion synthesis polymerases (B), or both.
See this image and copyright information in PMC

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