DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that in humans is encoded by the PRKDC gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase

Phosphatidylinositol 3-kinase-related kinase

Phosphatidylinositol 3-kinase-related kinases are a family of Ser/Thr-protein kinases with sequence similarity to phosphatidylinositol-3 kinases .- Members :The human PIKK family includes six members:- Structure :...

 protein family.

Function

DNA-PKcs is the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase

Serine/threonine-specific protein kinase

Serine/threonine protein kinases phosphorylate the OH group of serine or threonine .At least 125 of the 500+ human protein kinases are serine/threonine kinases .-Regulation:...

 called DNA-PK. The second component is the autoimmune antigen Ku

Ku (protein)

Ku is a protein that binds to DNA double-strand break ends and is required for the non-homologous end joining pathway of DNA repair. Ku is evolutionarily conserved from bacteria to human. The ancestral bacterial Ku is a homodimer...

. On its own, DNA-PKcs is inactive and relies on Ku to direct it to DNA ends and trigger its kinase activity DNA-PKcs is required for the non-homologous end joining

Non-homologous end joining

Non-homologous end joining is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homologous recombination, which requires a homologous sequence to guide...

 (NHEJ) pathway of DNA repair

DNA repair

DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...

, which rejoins double-strand breaks. It is also required for V(D)J recombination

V(D)J recombination

VJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...

, a process that utilizes NHEJ to promote immune system diversity. DNA-PKcs knockout mice have severe combined immunodeficiency

Severe combined immunodeficiency (non-human)

Severe Combined Immunodeficiency is a severe immunodeficiency genetic disorder that is characterized by the complete inability of the adaptive immune system to mount, coordinate, and sustain an appropriate immune response, usually due to absent or atypical T and B lymphocytes...

 due to their V(D)J recombination defect.

Many proteins have been identified as substrates for the kinase activity of DNA-PK. Autophosphorylation of DNA-PKcs appears to play a key role in NHEJ and is thought to induce a conformational change that allows end processing enzymes to access the ends of the double-strand break. DNA-PK also cooperates with ATR

Ataxia telangiectasia and Rad3 related

Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein or FRAP-related protein 1 is an enzyme that in humans is encoded by the ATR gene...

 and ATM

Ataxia telangiectasia mutated

Ataxia telangiectasia mutated is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis...

 to phosphorylate

Phosphorylation

Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....

 proteins involved in the DNA damage checkpoint

Cell cycle checkpoint

Cell cycle checkpoints are control mechanisms that ensure the fidelity of cell division in eukaryotic cells. These checkpoints verify whether the processes at each phase of the cell cycle have been accurately completed before progression into the next phase...

.

Interactions

DNA-PKcs has been shown to interact

Protein-protein interaction

Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

 with NCOA6

NCOA6

Nuclear receptor coactivator 6 is a protein that in humans is encoded by the NCOA6 gene.-Interactions:NCOA6 has been shown to interact with Ku70, RBBP5, E2F1, Retinoblastoma protein, CREB-binding protein, Activating transcription factor 2, HSF1, HBXIP, TGS1, TUBB, TUBA4A, Thyroid hormone receptor...

, CHEK1

CHEK1

Serine/threonine-protein kinase Chk1 is an enzyme that in humans is encoded by the CHEK1 gene.Chk1 is a kinase that phosphorylates cdc25, an important phosphatase in cell cycle control, particularly for entry into mitosis. Cdc25, when phosphorylated on serine 216 by chk1 becomes bound by an adaptor...

, Werner syndrome ATP-dependent helicase, RPA2

RPA2

Replication protein A 32 kDa subunit is a protein that in humans is encoded by the RPA2 gene.-Interactions:RPA2 has been shown to interact with Ku70, Replication protein A1, RPA3, DNA-PKcs, STAT3, Cyclin O, MEN1, TP53BP1 and Uracil-DNA glycosylase....

, ILF3

ILF3

Interleukin enhancer-binding factor 3 is a protein that in humans is encoded by the ILF3 gene.-Interactions:ILF3 has been shown to interact with XPO5, FUS, Protein kinase R, PRMT1 and DNA-PKcs....

, DCLRE1C

DCLRE1C

Protein artemis is a protein that in humans is encoded by the DCLRE1C gene.- Function :This gene encodes a nuclear protein that is involved in VJ recombination and DNA repair...

, ILF2

ILF2

Interleukin enhancer-binding factor 2 is a protein that in humans is encoded by the ILF2 gene.-Interactions:ILF2 has been shown to interact with CDC5L and DNA-PKcs....

, Ataxia telangiectasia mutated

Ataxia telangiectasia mutated

Ataxia telangiectasia mutated is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis...

, Ku80, CDC5L

CDC5L

Cell division cycle 5-like protein is a protein that in humans is encoded by the CDC5L gene.-Interactions:CDC5L has been shown to interact with SRRM1, RPS25, SF3B1, ILF2, CWC15, DNA-PKcs, GCN1L1, BZW1, TTF2, SF3B2, SFRS2, ASF/SF2, PLRG1, DYNC1H1, PPP1CA, Small nuclear ribonucleoprotein D1, SF3B4,...

, P53

P53

p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

, CIB1

CIB1

Calcium and integrin-binding protein 1 is a protein that in humans is encoded by the CIB1 gene.-Interactions:CIB1 has been shown to interact with RAC3, PSEN2, DNA-PKcs, UBR5 and CD61.-Further reading:...

, C1D

C1D

Nuclear nucleic acid-binding protein C1D is a protein that in humans is encoded by the C1D gene.-Interactions:C1D has been shown to interact with TSNAX and DNA-PKcs.-Further reading:...

 and CHUK

CHUK

Inhibitor of nuclear factor kappa-B kinase subunit alpha also known as IKK1 or conserved helix-loop-helix ubiquitous kinase is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription...

.

See also

• Non-homologous end joining
  Non-homologous end joining
  Non-homologous end joining is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homologous recombination, which requires a homologous sequence to guide...
  
  
• V(D)J recombination
  V(D)J recombination
  VJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...
  
  
• Ku
  Ku (protein)
  Ku is a protein that binds to DNA double-strand break ends and is required for the non-homologous end joining pathway of DNA repair. Ku is evolutionarily conserved from bacteria to human. The ancestral bacterial Ku is a homodimer...
  
  
• Protein kinase
  Protein kinase
  A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...