Mechanisms of interstrand DNA crosslink repair

Interstrand crosslinks (ICLs) are an extremely toxic class of DNA damage incurred during normal metabolism or cancer chemotherapy.  ICLs covalently tether both strands of duplex DNA, preventing strand unwinding essential for polymerase access. In this project we are focused on how the strand cleavages are made to resolve an interstrand DNA crosslink. We study the related structure-specific endonucleases Ercc1-Xpf and Mus81-Eme1, as well as the link to DNA replication and homologous recombination. 

Mechanism of interstrand DNA crosslink repair

Interstrand crosslinks (ICLs) are an extremely toxic class of DNA damage incurred during normal metabolism or cancer chemotherapy.  ICLs covalently tether both strands of duplex DNA, preventing strand unwinding essential for polymerase access. In this project we are focused on how the strand cleavages are made to resolve an interstrand DNA crosslink. We study the related structure-specific endonucleases Ercc1-Xpf and Mus81-Eme1, as well as the link to DNA replication and homologous recombination. 

See also:

Hanada et al.  (2006).  The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA cross-links into double-strands breaks.  EMBO J. 25, 4921-4932.

Niedernhofer et al.  (2004).  The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand crosslink-induced double-strand breaks.  Mol. Cell. Biol. 24, 5776-5787.