POLL
Encyclopedia
DNA polymerase lambda, also known as POLL, is a protein
that, in humans, is encoded by the POLLA gene
.
s. It is thought to resynthesize missing nucleotides during non-homologous end joining
, a pathway of DNA double-strand break repair. The crystal structure of pol λ shows that, unlike the DNA polymerases that catalyze DNA replication
, pol λ makes extensive contacts with the 5' phosphate of the downstream DNA strand. This allows the polymerase to stabilize the two ends of a double-strand break and explains how pol λ is uniquely suited for a role in non-homologous end joining. In addition to NHEJ, pol λ can also participate in base excision repair
, where it provides backup activity in the absence of Pol β
.
Besides its catalytic polymerase domain, pol λ has an 8 kDa domain and a BRCT domain
. The 8 kDa domain has lyase activity that can remove a 5' deoxyribosephosphate group from the end of a strand break. The BRCT domain is a phosphopeptide binding domain that is common among DNA repair proteins and is likely involved in coordinating protein-protein interactions. Pol λ is structurally and functionally related to pol μ, another member of the X family that also participates in non-homologous end joining
. Like pol μ, pol λ participates in V(D)J recombination, the process by which B-cell
and T-cell receptor diversity is generated in the vertebrate
immune system
. Whereas pol μ is important for heavy-chain rearrangements, pol λ seems to be more important for light-chain rearrangements. The yeast Saccharomyces cerevisiae
has a single homolog of both pol λ and pol μ called Pol4.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the POLLA 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...
.
Function
Pol λ is a member of the X family of DNA polymeraseDNA polymerase
A DNA polymerase is an enzyme that helps catalyze in the polymerization of deoxyribonucleotides into a DNA strand. DNA polymerases are best known for their feedback role in DNA replication, in which the polymerase "reads" an intact DNA strand as a template and uses it to synthesize the new strand....
s. It is thought to resynthesize missing nucleotides during 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...
, a pathway of DNA double-strand break repair. The crystal structure of pol λ shows that, unlike the DNA polymerases that catalyze DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
, pol λ makes extensive contacts with the 5' phosphate of the downstream DNA strand. This allows the polymerase to stabilize the two ends of a double-strand break and explains how pol λ is uniquely suited for a role in non-homologous end joining. In addition to NHEJ, pol λ can also participate in base excision repair
Base excision repair
In biochemistry and genetics, base excision repair is a cellular mechanism that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky...
, where it provides backup activity in the absence of Pol β
DNA polymerase beta
[edit]Polymerase , beta, also known as POLB, is an enzyme that, in humans, is encoded by the POLB gene.- Function :...
.
Besides its catalytic polymerase domain, pol λ has an 8 kDa domain and a BRCT domain
BRCT domain
BRCA1 C Terminus domain is a family of evolutionarily related proteins.The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage, for example as found in the breast cancer DNA-repair protein BRCA1...
. The 8 kDa domain has lyase activity that can remove a 5' deoxyribosephosphate group from the end of a strand break. The BRCT domain is a phosphopeptide binding domain that is common among DNA repair proteins and is likely involved in coordinating protein-protein interactions. Pol λ is structurally and functionally related to pol μ, another member of the X family that also participates in 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...
. Like pol μ, pol λ participates in V(D)J recombination, the process by which B-cell
B-cell receptor
The B-cell receptor is a transmembrane receptor protein located on the outer surface of B-cells. The receptor's binding moiety is composed of a membrane-bound antibody that, like all antibodies, has a unique and randomly-determined antigen-binding site...
and T-cell receptor diversity is generated in the vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. Whereas pol μ is important for heavy-chain rearrangements, pol λ seems to be more important for light-chain rearrangements. The yeast Saccharomyces cerevisiae
Saccharomyces cerevisiae
Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...
has a single homolog of both pol λ and pol μ called Pol4.