Abstract:
:To address how eukaryotic replication forks respond to fork stalling caused by strong non-covalent protein-DNA barriers, we engineered the controllable Fob-block system in Saccharomyces cerevisiae. This system allows us to strongly induce and control replication fork barriers (RFB) at their natural location within the rDNA. We discover a pivotal role for the MRX (Mre11, Rad50, Xrs2) complex for fork integrity at RFBs, which differs from its acknowledged function in double-strand break processing. Consequently, in the absence of the MRX complex, single-stranded DNA (ssDNA) accumulates at the rDNA. Based on this, we propose a model where the MRX complex specifically protects stalled forks at protein-DNA barriers, and its absence leads to processing resulting in ssDNA. To our surprise, this ssDNA does not trigger a checkpoint response. Intriguingly, however, placing RFBs ectopically on chromosome VI provokes a strong Rad53 checkpoint activation in the absence of Mre11. We demonstrate that proper checkpoint signalling within the rDNA is restored on deletion of SIR2. This suggests the surprising and novel concept that chromatin is an important player in checkpoint signalling.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Bentsen IB,Nielsen I,Lisby M,Nielsen HB,Gupta SS,Mundbjerg K,Andersen AH,Bjergbaek Ldoi
10.1093/nar/gkt051subject
Has Abstractpub_date
2013-03-01 00:00:00pages
3173-89issue
5eissn
0305-1048issn
1362-4962pii
gkt051journal_volume
41pub_type
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journal_title:Nucleic acids research
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