Structure of the RecQ C-terminal domain of human Bloom syndrome protein.

[werner syndrome]

Bloom syndrome is a rare genetic disorder characterized by genomic instability and cancer predisposition . The disease is caused by mutations of the Bloom syndrome protein (BLM ). Here we report the crystal structure of a RecQ C-terminal (RQC ) domain from human BLM . The structure reveals three novel features of BLM RQC which distinguish it from the previous structures of the Werner syndrome protein (WRN ) and RECQ 1 . First , BLM RQC lacks an aromatic residue at the tip of the β-wing , a key element of the RecQ-family helicases used for DNA-strand separation . Second , a BLM -specific insertion between the N-terminal helices exhibits a looping-out structure that extends at right angles to the β-wing . Deletion mutagenesis of this insertion interfered with binding to Holliday junction . Third , the C-terminal region of BLM RQC adopts an extended structure running along the domain surface , which may facilitate the spatial positioning of an HRDC domain in the full-length protein .