Biology Reference
In-Depth Information
Nonhomologous end joining
3
¢
Single-strand annealing
Ligation
3
¢
DNA damage
Resection
5
¢
-3
¢
Resection
Alternative nonhomologous end joining
3
¢
3
¢
Resection
Direct repeat
annealing
D-loop formation
Microhomology annealing
DNA synthesis
Ligation
Ligation
Synthesis-dependent strand annealing
D-loop cleavage
D-loo
p dissociation
DNA synthesis
DNA synthesis
Ligation
Noncrossover
Crossover
F
IG
. 2. Alternative double-strand break repair (DSBR) mechanisms. Nonhomologous end-
joining (NHEJ) or alternative NHEJ (Alt-NHEJ) occurs by either direct ligation of the broken
DNA strand or ligation after minimal processing. Both NHEJ and Alt-NHEJ are error-prone repair
mechanisms. DSBR within direct repeat sequences could occur by single-strand annealing (SSA).
SSA causes loss of a repeat sequence due to direct resection, annealing, and ligation. During DSBR
through synthesis-dependent strand annealing (SDSA), synthesized nascent strand is displaced by
D-loop dissociation, and anneals with the other 3
0
ssDNA overhang to complete DNA synthesis.
SDSA results in noncrossover products. After the initial D-loop formation and DNA synthesis, the
D-loop can also be cleaved to produce crossover products.
As discussed, HR is a template-dependent repair process and was long ago
recognized to require the formation of a DNA crossover structure at the site of
homology between chromosomes (termed Holliday junction; Ref.
30
). In the
1980s, a DSB repair model that involves the formation of a double Holliday
junction (dHJ) was developed based on transformation studies in budding yeast
(
Saccharomyces cerevisiae
), where a linear plasmid was faithfully integrated
into a homologous region of the host genome (
Fig. 1
; Refs.
31,32
). Even though
the DSB repair model also explains meiotic recombination products, during
mitotic recombination very few crossover events are observed since the sister
chromatid appears to be largely used as the template. The use of a sister
chromatid strongly suggests that mitotic recombination mainly occurs during
