DNA polymerase lambda

Polymerase (DNA directed), lambda

Rendering based on 1xsn of pol ? bound to a DNA strand containing a 1-nt gap.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols POLL ; BETAN; POLKAPPA
External IDs OMIM: 606343 MGI: 1889000 HomoloGene: 40863 ChEMBL: 5367 GeneCards: POLL Gene
EC number 2.7.7.7
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 27343 56626
Ensembl ENSG00000166169 ENSMUSG00000025218
UniProt Q9UGP5 Q9QXE2
RefSeq (mRNA) NM_001174084 NM_020032
RefSeq (protein) NP_001167555 NP_064416
Location (UCSC) Chr 10:
101.58 – 101.59 Mb		 Chr 19:
45.55 – 45.56 Mb
PubMed search

DNA polymerase lambda, also known as POLL, is a protein that, in humans, is encoded by the POLLA gene.[1][2]

Function

Pol λ is a member of the X family of DNA polymerases. It is thought to resynthesize missing nucleotides during non-homologous end joining, a pathway of DNA double-strand break repair.[3][4] 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.[5] In addition to NHEJ, pol λ can also participate in base excision repair, where it provides backup activity in the absence of Pol β.[6][7]

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.[8] The BRCT domain is a phosphopeptide binding domain that is common among DNA repair proteins and is likely involved in coordinating protein-protein interactions.[9] Pol λ is structurally and functionally related to pol μ, another member of the X family that also participates in non-homologous end joining.[10] 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.[11][12] The yeast Saccharomyces cerevisiae has a single homolog of both pol λ and pol μ called Pol4.[13]

Interactions

Pol λ has been shown to interact with PCNA.[14]

References

  1. ↑ "Entrez Gene: POLL polymerase (DNA directed), lambda".
  2. ↑ Aoufouchi S, Flatter E, Dahan A, Faili A, Bertocci B, Storck S, Delbos F, Cocea L, Gupta N, Weill JC, Reynaud CA (September 2000). "Two novel human and mouse DNA polymerases of the polX family". Nucleic Acids Res. 28 (18): 3684–93. doi:10.1093/nar/28.18.3684. PMC 110747. PMID 10982892.
  3. ↑ Daley JM, Laan RL, Suresh A, Wilson TE (August 2005). "DNA joint dependence of pol X family polymerase action in nonhomologous end joining". J. Biol. Chem. 280 (32): 29030–7. doi:10.1074/jbc.M505277200. PMID 15964833.
  4. ↑ Lee JW, Blanco L, Zhou T, Garcia-Diaz M, Bebenek K, Kunkel TA, Wang Z, Povirk LF (January 2004). "Implication of DNA polymerase lambda in alignment-based gap filling for nonhomologous DNA end joining in human nuclear extracts". J. Biol. Chem. 279 (1): 805–11. doi:10.1074/jbc.M307913200. PMID 14561766.
  5. ↑ Garcia-Diaz M, Bebenek K, Krahn JM, Blanco L, Kunkel TA, Pedersen LC (February 2004). "A structural solution for the DNA polymerase lambda-dependent repair of DNA gaps with minimal homology". Mol. Cell 13 (4): 561–72. doi:10.1016/S1097-2765(04)00061-9. PMID 14992725.
  6. ↑ Tano K, Nakamura J, Asagoshi K, Arakawa H, Sonoda E, Braithwaite EK, Prasad R, Buerstedde JM, Takeda S, Watanabe M, Wilson SH (June 2007). "Interplay between DNA polymerases beta and lambda in repair of oxidation DNA damage in chicken DT40 cells". DNA Repair (Amst.) 6 (6): 869–75. doi:10.1016/j.dnarep.2007.01.011. PMC 2080795. PMID 17363341.
  7. ↑ Braithwaite EK, Prasad R, Shock DD, Hou EW, Beard WA, Wilson SH (May 2005). "DNA polymerase lambda mediates a back-up base excision repair activity in extracts of mouse embryonic fibroblasts". J. Biol. Chem. 280 (18): 18469–75. doi:10.1074/jbc.M411864200. PMID 15749700.
  8. ↑ García-Díaz M, Bebenek K, Kunkel TA, Blanco L (September 2001). "Identification of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in human DNA polymerase lambda: a possible role in base excision repair". J. Biol. Chem. 276 (37): 34659–63. doi:10.1074/jbc.M106336200. PMID 11457865.
  9. ↑ Yu X, Chini CC, He M, Mer G, Chen J (October 2003). "The BRCT domain is a phospho-protein binding domain". Science 302 (5645): 639–42. doi:10.1126/science.1088753. PMID 14576433.
  10. ↑ Nick McElhinny SA, Ramsden DA (August 2004). "Sibling rivalry: competition between Pol X family members in V(D)J recombination and general double strand break repair". Immunol. Rev. 200: 156–64. doi:10.1111/j.0105-2896.2004.00160.x. PMID 15242403.
  11. ↑ Bertocci B, De Smet A, Berek C, Weill JC, Reynaud CA (August 2003). "Immunoglobulin kappa light chain gene rearrangement is impaired in mice deficient for DNA polymerase mu". Immunity 19 (2): 203–11. doi:10.1016/S1074-7613(03)00203-6. PMID 12932354.
  12. ↑ Bertocci B, De Smet A, Weill JC, Reynaud CA (July 2006). "Nonoverlapping functions of DNA polymerases mu, lambda, and terminal deoxynucleotidyltransferase during immunoglobulin V(D)J recombination in vivo". Immunity 25 (1): 31–41. doi:10.1016/j.immuni.2006.04.013. PMID 16860755.
  13. ↑ Lieber MR (July 2006). "The polymerases for V(D)J recombination". Immunity 25 (1): 7–9. doi:10.1016/j.immuni.2006.07.007. PMID 16860749.
  14. ↑ Maga G, Villani G, Ramadan K, Shevelev I, Tanguy Le Gac N, Blanco L, Blanca G, Spadari S, Hübscher U (December 2002). "Human DNA polymerase lambda functionally and physically interacts with proliferating cell nuclear antigen in normal and translesion DNA synthesis". J. Biol. Chem. 277 (50): 48434–40. doi:10.1074/jbc.M206889200. PMID 12368291.


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