FANCM: fork pause, rewind and play.
DNA lesions or genomic regions that are difficult to traverse frequently hinder or block DNA replication. In response to replication fork stalling, the cell activates the replication stress response pathway, which acts to protect the fork from collapse, promotes the repair or bypass of the blockage and facilitates the resumption of DNA synthesis. In this issue of the EMBO Journal, two studies conducted by the Constantinou and Niedzwiedz laboratories shed light on how the DNA translocase FANCM acts to regulate the replication stress response (Luke-Glaser et al, 2009; Schwab et al, 2009). These studies help to explain how FANCM (mutated in the human cancer predisposition syndrome, Fanconi's anaemia (FA)) co-ordinately regulates checkpoint signalling and replication fork progression.
Collis
Spencer J
SJ
Genome Stability Group, YCR Institute for Cancer Studies, University of Sheffield Medical School, Sheffield, UK.
Boulton
Simon J
SJ
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction
D018797:Cell Cycle Proteins; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C518295:FANCM protein, human; D004265:DNA Helicases