Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene. [5] [6]
Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene. [5] [6]
The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. [7]
In somatic cells the RAD9-RAD1-HUS1 (9-1-1) complex responds to DNA damage by promoting DNA repair. [8]
In flies, worms and yeast, the 9-1-1 complex is necessary for meiotic checkpoint function and efficient meiotic recombination. [8] During mammalian meiosis 9-1-1 complexes promote synapsis of homologous chromosomes, double-strand break repair and cell cycle checkpoint signalling. [8] [9]
HUS1 has been shown to interact with:
Werner syndrome ATP-dependent helicase, also known as DNA helicase, RecQ-like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. Helicase enzymes generally unwind and separate double-stranded DNA. These activities are necessary before DNA can be copied in preparation for cell division. Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription. Further evidence suggests that Werner protein plays a critical role in repairing DNA. Overall, this protein helps maintain the structure and integrity of a person's DNA.
Proliferating cell nuclear antigen (PCNA) is a DNA clamp that acts as a processivity factor for DNA polymerase δ in eukaryotic cells and is essential for replication. PCNA is a homotrimer and achieves its processivity by encircling the DNA, where it acts as a scaffold to recruit proteins involved in DNA replication, DNA repair, chromatin remodeling and epigenetics.
A DNA clamp, also known as a sliding clamp, is a protein complex that serves as a processivity-promoting factor in DNA replication. As a critical component of the DNA polymerase III holoenzyme, the clamp protein binds DNA polymerase and prevents this enzyme from dissociating from the template DNA strand. The clamp-polymerase protein–protein interactions are stronger and more specific than the direct interactions between the polymerase and the template DNA strand; because one of the rate-limiting steps in the DNA synthesis reaction is the association of the polymerase with the DNA template, the presence of the sliding clamp dramatically increases the number of nucleotides that the polymerase can add to the growing strand per association event. The presence of the DNA clamp can increase the rate of DNA synthesis up to 1,000-fold compared with a nonprocessive polymerase.
Serine/threonine-protein kinase ATR, also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1), is an enzyme that, in humans, is encoded by the ATR gene. It is a large kinase of about 301.66 kDa. ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family. ATR is activated in response to single strand breaks, and works with ATM to ensure genome integrity.
Cell cycle checkpoint control protein RAD9A is a protein that in humans is encoded by the RAD9A gene.Rad9 has been shown to induce G2 arrest in the cell cycle in response to DNA damage in yeast cells. Rad9 was originally found in budding yeast cells but a human homolog has also been found and studies have suggested that the molecular mechanisms of the S and G2 checkpoints are conserved in eukaryotes. Thus, what is found in yeast cells are likely to be similar in human cells.
Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene.
Flap endonuclease 1 is an enzyme that in humans is encoded by the FEN1 gene.
ATP-dependent RNA helicase A is an enzyme that in humans is encoded by the DHX9 gene.
Cell cycle checkpoint protein RAD1 is a protein that in humans is encoded by the RAD1 gene.
Replication factor C subunit 1 is a protein that in humans is encoded by the RFC1 gene.
Cyclin-O is a protein that in humans is encoded by the CCNO gene.
Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene.
Replication factor C subunit 4 is a protein that in humans is encoded by the RFC4 gene.
Replication factor C subunit 2 is a protein that in humans is encoded by the RFC2 gene.
Replication factor C subunit 3 is a protein that in humans is encoded by the RFC3 gene.
Replication factor C subunit 5 is a protein that in humans is encoded by the RFC5 gene.
Claspin is a protein that in humans is encoded by the CLSPN gene.
Sister chromatid cohesion protein DCC1 is a protein that in humans is encoded by the DSCC1 gene.
Chromosome transmission fidelity protein 18 homolog is a protein that in humans is encoded by the CHTF18 gene.
Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein in archaea.