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 signa...

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Bibliographic Details
Published in:Chromosoma 2010-04, Vol.119 (2), p.115-135
Main Authors: Rupnik, Agnieszka, Lowndes, Noel F, Grenon, Muriel
Format: Article
Language:English
Subjects:
Acid Anhydride Hydrolases
Animal Genetics and Genomics
Animals
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Cycle Proteins - physiology
Developmental Biology
DNA - genetics
DNA - metabolism
DNA Breaks, Double-Stranded
DNA Repair
DNA Repair Enzymes - chemistry
DNA Repair Enzymes - physiology
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - physiology
Eukaryotic Microbiology
Human Genetics
Humans
Life Sciences
MRE11 Homologue Protein
Nuclear Proteins - physiology
Protein Processing, Post-Translational
Review
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Summary: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.
ISSN:0009-5915
1432-0886
DOI:10.1007/s00412-009-0242-4