RecA family proteins are the central recombinases for HR. The family
includes prokaryotic RecA, archaeal RadA, and eukaryotic Rad51 and
Dmc1. They have important roles in cell proliferation, genome
maintenance, and genetic diversity, particularly in higher eukaryotes.
For example, Rad51-deficient vertebrate cells accumulate chromosomal
breaks before death. Rad51 and its meiosis-specific homolog, Dmc1, are
also indispensable for meiosis, a specialized cell cycle for
production of gametes. Mammalian Rad51 and Dmc1 proteins are known to
interact with tumor suppressor proteins such as BRCA2.
Since scientists discovered RecA family proteins, it has been assumed
that RecA (and other homologs) forms only 61 right-handed filaments (six
protein monomers per helical turn), and then hydrolyzes ATP to promote
HR and recombinational DNA repair. Whereas a controversial puzzle came
out, how the energy of ATP facilitating DNA rotation during the strand
exchange reaction.
By X-ray crystallography and atomic force microscopy approaches, Dr.
Wangs� team provided the answer. They reported that archaeal
Sulfolobus solfataricus RadA proteins can also self-polymerize into a
31 right-handed filament with 3 monomers per helical turn (reported in
PLoS ONE) and a 43 right-handed helical filament with 4 monomers per
helical turn (reported in Nucleic Acids Research).
Additional biophysical and biochemical analyses revealed that RecA
family proteins may couple ATP binding and hydrolysis to the DNA
strand exchange reaction in a manner that promotes clockwise axial
rotation of nucleoprotein filaments. Specially, the 61 RadA helical
filament undergoes clockwise axial rotation in 2 discrete 120� steps
to the 31 extended right-handed filament and then to the 43
left-handed filament. As a result, all the DNA-binding motifs (denoted
L1, L2 and HhH) in the RadA proteins move concurrently to mediate DNA
binding, homology pairing, and strand exchange, respectively.
Therefore, the energy of ATP is used to rotate not only DNA substrates
but also the RecA family protein filaments.
This new model is in contrast to all current hypotheses, which
overlooks the fact that RecA family proteins are flexible enough to
form both right-handed and left-handed helical filaments. From this
perspective, these researchers in Taiwan have opened a new avenue for
understanding the molecular mechanisms of RecA family proteins.
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