The Bloom's syndrome gene product promotes branch migration of Holliday junctions
AUTOR(ES)
Karow, Julia K.
FONTE
National Academy of Sciences
RESUMO
Bloom's syndrome (BS) is an autosomal recessive disorder associated with dwarfism, immunodeficiency, reduced fertility, and elevated levels of many types of cancer. BS cells show marked genomic instability; in particular, hyperrecombination between sister chromatids and homologous chromosomes. This instability is thought to result from defective processing of DNA replication intermediates. The gene mutated in BS, BLM, encodes a member of the RecQ family of DExH box DNA helicases, which also includes the Werner's syndrome gene product. We have investigated the mechanism by which BLM suppresses hyperrecombination. Here, we show that BLM selectively binds Holliday junctions in vitro and acts on recombination intermediates containing a Holliday junction to promote ATP-dependent branch migration. We present a model in which BLM disrupts potentially recombinogenic molecules that arise at sites of stalled replication forks. Our results have implications for the role of BLM as an anti-recombinase in the suppression of tumorigenesis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18638Documentos Relacionados
- Direct association of Bloom’s syndrome gene product with the human mismatch repair protein MLH1
- Direct observation of RuvAB-catalyzed branch migration of single Holliday junctions
- Observing spontaneous branch migration of Holliday junctions one step at a time
- A method for preparing genomic DNA that restrains branch migration of Holliday junctions
- RuvAB-directed branch migration of individual Holliday junctions is impeded by sequence heterology