MRN and the race to the break.
In all living cells, DNA is constantly threatened by both endogenous and exogenous agents. In order to protect genetic information, all cells have developed a sophisticated network of proteins, which constantly monitor genomic integrity. This network, termed the DNA damage response, senses and signals the presence of DNA damage to effect numerous biological responses, including DNA repair, transient cell cycle arrests ("checkpoints") and apoptosis. The MRN complex (MRX in yeast), composed of Mre11, Rad50 and Nbs1 (Xrs2), is a key component of the immediate early response to DNA damage, involved in a cross-talk between the repair and checkpoint machinery. Using its ability to bind DNA ends, it is ideally placed to sense and signal the presence of double strand breaks and plays an important role in DNA repair and cellular survival. Here, we summarise recent observation on MRN structure, function, regulation and emerging mechanisms by which the MRN nano-machinery protects genomic integrity. Finally, we discuss the biological significance of the unique MRN structure and summarise the emerging sequence of early events of the response to double strand breaks orchestrated by the MRN complex.
Centre for Chromosome Biology, School of Natural Science, National University of Ireland Galway, University Road, Galway, Ireland.
Agnieszka
A
Rupnik
Noel F
NF
Lowndes
Muriel
M
Grenon
D017766:Acid Anhydride Hydrolases; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000502:physiology*; D011499:Protein Processing, Post-Translational
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D004247:DNA; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes