BRG1 co-localizes with DNA replication factors and is required for efficient replication fork progression.
For DNA replication to occur, chromatin must be remodeled. Yet, we know very little about which proteins alter nucleosome occupancy at origins and replication forks and for what aspects of replication they are required. Here, we demonstrate that the BRG1 catalytic subunit of mammalian SWI/SNF-related complexes co-localizes with origin recognition complexes, GINS complexes, and proliferating cell nuclear antigen at sites of DNA replication on extended chromatin fibers. The specific pattern of BRG1 occupancy suggests it does not participate in origin selection but is involved in the firing of origins and the process of replication elongation. This latter function is confirmed by the fact that Brg1 mutant mouse embryos and RNAi knockdown cells exhibit a 50% reduction in replication fork progression rates, which is associated with decreased cell proliferation. This novel function of BRG1 is consistent with its requirement during embryogenesis and its role as a tumor suppressor to maintain genome stability and prevent cancer.
Cohen
Stephanie M
SM
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Chastain
Paul D
PD
Rosson
Gary B
GB
Groh
Beezly S
BS
Weissman
Bernard E
BE
Kaufman
David G
DG
Bultman
Scott J
SJ
D000818:Animals; D049109:Cell Proliferation; D002843:Chromatin / Q000737:chemistry; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000032:analysis; D047108:Embryonic Development; D041905:Erythroid Cells / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases