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The Functional Role of the Mre11 Dimeric Interface
Author(s) -
Albrecht Dustin,
Herdendorf Timothy,
Nelson Scott
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.536.6
Subject(s) - rad50 , exonuclease , nuclease , chemistry , dna , endonuclease , dimer , helicase , atp hydrolysis , recbcd , biophysics , dna repair , microbiology and biotechnology , biochemistry , biology , enzyme , dna binding protein , atpase , dna polymerase , rna , gene , organic chemistry , transcription factor
The Mre11/Rad50 (MR) complex is a central player in DNA repair and is implicated in the processing of DNA ends caused by damage‐induced double strand breaks. Rad50 is a member of the ABC protein family, which are dimeric enzymes that bind and hydrolyze ATP. Mre11 is a ssDNA endonuclease and a dsDNA exonuclease that forms a heterotetrameric complex (M2/R2) with Rad50. Recent structures indicate that the MR complex undergoes extensive conformational rearrangements during ATP hydrolysis and nucleotide excision. Notably, two forms of the Mre11 dimer interface have been observed, denoted here as ‘open’ and closed’. In order to understand the significance of these two states, we have generated and characterized a bacteriophage T4 Mre11 mutant (Mre11L101D) that is expected to disrupt the closed form of the Mre11 dimer. The variety of functional assays suggest that the Mre11 dimer interface undergoes ATP‐driven conformational rearrangements (i.e., an opening and closing) during the nuclease reaction cycle. Productive complex assembly and the nucleolytic reaction occur when Mre11 is in the open state, whereas translocation of the MR along the DNA substrate requires formation of the closed state.