POLA1 Curator Discussion (Retired)

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Quality control issues for polA1 annotations; Checked annotation summary graphs from 16.11.2007


Functions

  • Human gene is annotated to 'sugar binding' based on reactivity with conA. Is this correct?

Pascale 09:01, 25 January 2008 (PST)

- ConA is a lectin and it is this that does the sugar binding, therefore I have removed the annotation to PolA. (Rachael 6 February 2008)


  • How universal are some functions? (ie, can they safely be ISS'ed):
    • nucleotide binding
    • pyrimidine nucleotide binding
    • purine nt binding
    • chromatin binding
    • DNA binding
    • double stranded DNA binding

Pascale 09:01, 25 January 2008 (PST)


  • protein heterodimerization activity

Pascale 09:01, 25 January 2008 (PST)



For the following:

  • alpha DNA polymerase activity
  • alpha DNA primase activity

If the complex 'alpha DNA ploymerase:primase complex' is correct, you expect polA to have a role in both functions? And the corresponding processes.

Pascale 09:01, 25 January 2008 (PST)


Perhaps the definitions of DNA primase activity needs tweaking?

GO:0003896 DNA primase activity Catalysis of the synthesis of a short RNA primer on a DNA template, providing a free 3'-OH that can be extended by DNA-directed DNA polymerases. Catalyzed by a DNA-directed RNA polymerase that forms a complex with alpha DNA polymerase.

As far as I am aware polymerases cannot INITIATE synthesis without the priming reaction, so maybe the 'initiation of synthesis' should be part of the primase definition? I think this is why I have a strong objection to the annotation of DNA polymerase to 'primase'.

The assay may be showing that DNA polymerase can incorporate ribonucleotides as well as deoxyribonucleotides, or can increase the rate of the incorporation of ribonucleotides, but it does not appear to show that it has the ability to prime the reaction. Isn't this a key component of the primase function.?

If "priming" = primase reaction + primer extension

then the IDA could be to

GO:0006269 DNA replication, synthesis of RNA primer* Definition* The synthesis of a short RNA polymer, usually 4-15 nucleotides long, using one strand of unwound DNA as a template; the RNA then serves as a primer from which DNA polymerases extend synthesis. synonym replication priming

Val


Processes

  • Human gene is annotated to 'response to pH': in the original paper (PMID: 7504813), they demonstrated "that the fidelity of human DNA polymerase alpha increases 10-fold when the pH of the in vitro synthesis reaction is lowered from pH 8.6 to pH 6.1"

I think this annotation is wrong, and so are the two ISS (rat, chicken). Assaying enzyme activity at different pH measures a characteristic of the enzyme. The definition of 'response to pH is 'A change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a pH stimulus'. In this case they assays the enzyme in vitro, thus no conclusion can be made about the cellular response. Pascale 09:03, 25 January 2008 (PST)

- Agreed, the annotations to 'response to pH' to human, rat and chicken have been removed. (Rachael 6 February 2008)



  • Human gene is annotated top 'response to virus'. From abstract of PMID: 1848671

"We observed that the synthesis of ribonucleotide primers by DNA polymerase alpha-primase is dramatically stimulated by SV40 T antigen. The presence of T antigen also increased the average length of the DNA product synthesized on primed and unprimed single-stranded DNA templates."
The annotation seems wrong: the V40 T antigen stimulates DNA replication; but not the other way around. Pascale 09:03, 25 January 2008 (PST)

- Agreed, the annotation to 'response to virus' has been removed from human. (Rachael 6 February 2008)


  • Everyone

If you have a function annotation to DNA primase activity it means you can also make an annotation to: DNA replication synthesis of RNA primer (with the same evidence) There would be a process/function link between these 2 terms if we had them. Val

  • SGD:

I notice you have RNA -dependent DNA replication but this is for RNA template (i.e. what reverse transcriptase does)see: [ geneontology-Curator requests-1879833 ] RG: parent DNA replication RNA template Val

Components

  • alpha DNA ploymerase:primase complex (mouse, human, rat, fly, yeast, pombe) : Can this be applied to all other organisms?

Pascale 09:03, 25 January 2008 (PST)


Also, are the following expected to be universal? (some people have ISS'ed to those; I'd be comfortable to ISS to nucleus, but nothing more granular, unless there is evidence that those other components can reasonably be inferred for all eukaryotes>

  • chromatin
  • nucleoplasm
  • nuclear matrix
  • nucleolous

Pascale 09:03, 25 January 2008 (PST)