Figure 2: Mechanisms of genome instability arising through BIR
A: In normal replication forks, CMG is the helicase that unwinds dsDNA.
It has the ability to remove many types of impediments, including
RNA-DNA hybrids, RNA polymerases and other DNA-bound proteins with
minimal pausing, thereby allowing a fast progression of the replication
with short pausing times.
B: Break-induced replication
(BIR) forks are far more prone to template-switching and to instigate
non-allelic recombination, likely because the helicase activity of Pif1
alone is far less than that of the CMG complex with assistance from Pif1
and Rrm3, making BIR more prone to template-switch when encountering
impediments.
C: Proposed model for transcription-induced recombination at the
ribosomal DNA locus in budding yeast. Stabilised arrested forks can
sometimes erroneously be resumed by BIR; this could cause the encounter
of switching-prone BIR forks and elongating RNA pol I, leading to
template-switching, the formation of extrachromosomal ribosomal DNA
circles and copy-number variation of ribosomal DNA repeats.
D: Proposed model for CUP1 copy-number variation. When
encountering the scar left by a collapsed low-efficiency replication
origin inside the CUP1 repeats, a BIR fork could template-switch
to another CUP1 repeat and drive the formation of
extrachromosomal CUP1 circles and copy-number variation of CUP1repeats. Note that the replisome stalling event that precipitates BIR
does not need to be caused by transcription in this model, it is the
collapse of the low-efficiency origin that is caused by transcription.