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Based on the information gathered, I'll now provide a comprehensive review of GO-CAM model gomodel:617b481400000521 - "KAT5 involvement in nucleotide excision repair (Human)".

GO-CAM Model Review: KAT5 involvement in nucleotide excision repair (Human)

Model Overview

This model represents the role of KAT5 (TIP60) in nucleotide excision repair, specifically focusing on how it regulates the XPF-ERCC1 complex in human cells. The model is based on evidence from PMID:32034146.

Biological Content Assessment

Model Structure and Components

The model includes 4 key activities: 1. UniProtKB:Q96EB6 (SIRT1) - NAD-dependent protein lysine deacetylase activity (GO:0034979) 2. UniProtKB:Q92993 (KAT5/TIP60) - peptide-lysine-N-acetyltransferase activity (GO:0061733) 3. UniProtKB:Q92889-2 (ERCC4/XPF) - protein binding (GO:0005515) 4. UniProtKB:Q92889-2 (ERCC4/XPF) - single-stranded DNA endodeoxyribonuclease activity (GO:0000014)

Causal Relationships

  • SIRT1 deacetylase activity directly negatively regulates (RO:0002630) XPF protein binding activity
  • KAT5 acetyltransferase activity directly positively regulates (RO:0002629) XPF protein binding activity
  • XPF protein binding activity directly positively regulates (RO:0002629) XPF endonuclease activity

Biological Process Context

  • The XPF endonuclease activity and protein binding are part of nucleotide-excision repair (GO:0006289)

Scientific Accuracy and Consistency

The model accurately represents the findings from PMID:32034146, which reports that:

  1. TIP60 (KAT5) acetylates XPF at Lys911, which disrupts a salt bridge and facilitates XPF-ERCC1 complex assembly
  2. SIRT1 deacetylates XPF, counteracting TIP60's effect
  3. The acetylation of XPF is critical for proper nucleotide excision repair
  4. The activation of the XPF-ERCC1 complex through acetylation is essential for its function

Quality Assessment

Strengths

  1. The model correctly captures the core regulatory mechanism reported in the literature
  2. The causal relationships between activities are correctly represented using appropriate predicates
  3. The model includes both positive (KAT5) and negative (SIRT1) regulators of XPF activity
  4. All activities are appropriately part of the nucleotide excision repair biological process

Potential Issues and Recommendations

  1. Complex Representation Issue:
  2. The model uses Q92889-2 (ERCC4/XPF) for both protein binding and endonuclease activity, but the paper emphasizes that these activities are performed by the XPF-ERCC1 complex.

  3. Per the GO-CAM "How to annotate complexes" guideline, if the activity is specifically carried out by the complex rather than individual subunits, it would be better to use the complex ID (GO:0070522 "ERCC4-ERCC1 complex") to represent the endonuclease activity.

  4. Missing Components:

  5. While ERCC1 (UniProtKB:P07992) is listed in the objects of the model, it's not explicitly represented in the activities. Given the paper's emphasis on the importance of XPF-ERCC1 interaction for activity, it would be beneficial to represent ERCC1 more explicitly.

  6. Activity Annotation Specificity:

  7. The use of generic "protein binding" (GO:0005515) for XPF could be more specific, such as "protein complex binding" or even more specifically "ERCC1 binding" if such a term exists.

  8. Biological Context Expansion:

  9. The model could potentially include that TIP60 acetylation of XPF is induced by DNA damage (UV irradiation or MMC treatment), providing additional contextual information.

Recommendations for Improvement

  1. Consider using GO:0070522 (ERCC4-ERCC1 complex) as the entity for the endonuclease activity rather than just XPF protein, as the paper clearly shows this activity requires the complex.

  2. Add a representation of ERCC1's role in the complex, potentially showing it as part of the functional unit with XPF.

  3. Replace the generic "protein binding" term with a more specific term that better describes the XPF-ERCC1 interaction.

  4. Potentially expand the model to include the DNA damage context that induces TIP60 activation and subsequent XPF acetylation.

Overall Assessment

This is a well-structured model that captures the key findings from the paper regarding KAT5/TIP60's role in nucleotide excision repair through XPF acetylation. With minor adjustments to better represent the complex nature of the XPF-ERCC1 interaction, this model would provide an excellent representation of the biological pathway.