Biology Reference
In-Depth Information
FIGURE 7.1
Resection of DNA ends. A model primarily based on the studies on DNA end resection in yeast. The human homologues of the
yeast resection factors are depicted.
by the Sgs1 helicase. The 5
0
flaps generated at unwound
DNA ends are subsequently cleaved by the Dna2 endo-
nuclease. Thus, the coordinated action of Sgs1 and
Dna2 progressively resects the 5
0
ends of DSBs. In the
second mechanism, MRX recruits Sae2 to DNA ends.
9
The MRX-Sae2 complex has the ability to carry out
limited resection of the 5
0
ends. In addition, the MRX-
Sae2 complex recruits the Exo1 exonuclease to DNA
ends, promoting further 5
0
-to-3
0
resection by Exo1.
10
In
yeast, the MRX complex is important for the initiation
of resection, whereas Sgs1-Dna2 and Exo1 appear to
function redundantly in the extension of resection.
In human cells, the MRE11-RAD50-NBS1 (MRN)
complex, the homologue of yeast MRX, is needed for
efficient resection.
11,12
Human CtIP, the functional coun-
terpart of Sae2, is also important for the recruitment of
EXO1 and resection.
13,14
Like in yeast, human BLM heli-
case, the homologue of yeast Sgs1, functions in parallel
with EXO1 to promote DSB resection.
15
Formation of RAD51 Filament
Once ssDNA is generated by resection, it is first
recognized by the ssDNA-binding protein RPA. The
binding of RPA to ssDNA generates a key structure
