MRN:CtIP exonucleolytically hydrolyzes DNA 3' to SPO11 and SPO11:double-strand break dissociates to SPO11:oligonucleotide and resected 5' end

Stable Identifier
R-HSA-9023943
Type
Reaction [uncertain]
Species
Homo sapiens
Compartment
Synonyms
Removal of SPO11 and Resection of 5' Ends of DNA
General
SVG |   | PPTX  | SBGN
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The MRN complex (MRE11:RAD50:NBS1:CtIP) exonucleolytically hydrolyzes a single strand of DNA in a 3' to 5' direction starting at a single strand break made by the MRN complex 3' to SPO11.
SPO11 forms a dimer and each subunit cleaves a single strand of DNA, thus creating a double-strand break. After cleaving DNA, a SPO11 subunit remains covalently attached to each 5' end via a tyrosine residue. SPO11 is removed from the DNA by cleavage and exonucleolytic digestion of single strands 3' to the attached SPO11. The overall products are a resected 5' end (protruding 3' overhang) and a covalent complex of SPO11 with an oligonucleotide. Two size classes of oligonucleotide are observed: 12 to 26 nucleotides and 28 to 34 nucleotides. The enzyme responsible for excision of SPO11:oligonucleotide in mammals is inferred to be MRE11 in the MRE11:RAD50:NBS1:CtIP complex based on conservation of the reaction mechanism across yeast, plants, and animals (Sartori et al. 2007).
In fission and budding yeast the Mre11:Rad50:Xrs2/Nbs1 (MRN/MRX) complex is required for removal of SPO11. In human somatic cells the MRN complex together with CtIP resects double-strand breaks but the role of the MRN complex in mammalian meiosis, though essential, is unclear (Sartori et al. 2007).
After excision of SPO11:oligonucleotide the recessed 5' end is further resected by unknown exonucleases.

Literature References
PubMed ID Title Journal Year
17965729 Human CtIP promotes DNA end resection

Sartori, AA, Lukas, C, Coates, J, Mistrik, M, Fu, S, Bartek, J, Baer, R, Lukas, J, Jackson, SP

Nature 2007
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
3'-5'-exodeoxyribonuclease activity of MRN:CtIP [nucleoplasm]
Physical Entity
Activity
Inferred From
Authored
Reviewed
Created