#10942 GO:0071932 replication fork reversal

None
closed-rejected
5
2014-06-17
2014-06-16
No

Hello,

I am reading a paper on replication fork stalling, so I started looking at the child terms to "replication fork processing" (there aren't very many).

I was slightly unsure what this term meant: GO:0071932 replication fork reversal
but on a closer look I think this looks like a phenotype?

From the paper cited as a ref: rad53 mutants exhibit extensive single-stranded gaps and hemi-replicated intermediates, consistent with a lagging-strand synthesis defect. Further, rad53 cells accumulate Holliday junctions through fork reversal. We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability.

In the paper that I am reading right now, the authors say that normally when a fork is stalled, proteins act to protect the fork to prevent its collapse. If a fork does collapse, the fork may be restarted via homologous recomb but this is error prone and can lead to genomic instability.

So I guess in the ref for GO:0071932, replication fork stalling is abnormal, so they collapse and this leads to genomic instability? Does this sound right?

Discussion

  • Antonia Lock

    Antonia Lock - 2014-06-16

    also from PMID:
    23093942
    "Inappropriate ectopic recombination at arrested forks results in GCRs, whereas appropriate restarting of the fork on the initial template results in error-prone DNA synthesis."

     
  • Valerie Wood

    Valerie Wood - 2014-06-17

    I agree. I think I requested this term many year ago. I suggest it is obsoleted (only 3 EXP annotations)

    val

     
  • David Hill

    David Hill - 2014-06-17

    I have sent the obsoletion notice.

     
  • David Hill

    David Hill - 2014-06-17
    • assigned_to: David Hill
     
  • Jim Hu

    Jim Hu - 2014-06-17

    Fork reversal is not an abnormal phenotype. It's a normal process that responds to DNA damage that blocks fork progression. The forks are backed up to form Holliday-like structures that can be resolved to restart replication around a block. See, for example:

    http://www.sciencedirect.com/science/article/pii/S1097276501003586 and

    http://nar.oxfordjournals.org/content/37/11/3475.full

    What happens is that the replicative helicase gets ahead of the leading strand, when a lesion blocks leading strand progression. Reversing the fork and rewinding the DNA allows the lagging strand, which has progressed past the lesion, to form a 4-way junction with the end of the leading strand, forming a structure that is sometimes called a "chicken foot". This structure can be used for recombination to get past the lesion.

    I think we should be using this to annotate E. coli RecG.

    E. coli RecG helicase is a model for the helicases involved in this process.

     
  • David Hill

    David Hill - 2014-06-17
    • status: open --> closed-rejected
     
  • Valerie Wood

    Valerie Wood - 2014-06-17

    Thanks Jim, i was too hasty,
    val

     

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No, thanks