Molecular functions and cellular roles of the ChlR1 (DDX11) helicase defective in the rare cohesinopathy Warsaw breakage syndrome

摘要: In 2010, a new recessive cohesinopathy disorder, designated Warsaw breakage syndrome (WABS), was described. The individual with WABS displayed microcephaly, pre- and postnatal growth retardation, abnormal skin pigmentation. Cytogenetic analysis revealed mitomycin C (MMC)-induced chromosomal breakage; however, an additional sister chromatid cohesion defect also observed. is genetically linked to bi-allelic mutations in the ChlR1/DDX11 gene which encodes protein of conserved family Iron–Sulfur (Fe–S) cluster DNA helicases. Mutations budding yeast ortholog ChlR1, known as Chl1, were cause defects, indicating function gene. 2012, three affected siblings identified similar symptoms original case, found have homozygous mutation Fe–S domain confirming genetic linkage. Significantly, clinically relevant perturbed ChlR1 unwinding activity. addition its importance human disease, implicated papillomavirus genome maintenance cancer. Although precise functions homeostasis are still not well understood, ongoing molecular studies suggest helicase plays critically important role cellular replication and/or repair.