DNA polymerase lambda

POLL
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1NZP, 1RZT, 1XSL, 1XSN, 1XSP, 2BCQ, 2BCR, 2BCS, 2BCU, 2BCV, 2GWS, 2JW5, 2PFN, 2PFO, 2PFP, 2PFQ, 3C5F, 3C5G, 3HW8, 3HWT, 3HX0, 3MDA, 3MDC, 3MGH, 3MGI, 3PML, 3PMN, 3PNC, 3UPQ, 3UQ0, 3UQ2, 4FO6, 4K4G, 4K4H, 4K4I, 4XA5, 4XUS, 4X5V, 5CR0, 4XQ8, 5CJ7, 5DKW, 5CP2, 5DDY, 5DDM, 5CB1, 5CWR, 4XRH, 5CHG, 5CA7
Identifiers
Aliases	POLL, BETAN, POLKAPPA, polymerase (DNA) lambda, DNA polymerase lambda
External IDs	MGI: 1889000 HomoloGene: 40863 GeneCards: POLL
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q24.32 Start 101,578,882 bp[1] End 101,588,270 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 C3 Start 45,552,275 bp[2] End 45,560,531 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • DNA binding • nucleotidyltransferase activity • protein binding • metal ion binding • lyase activity • DNA-directed DNA polymerase activity • 5'-deoxyribose-5-phosphate lyase activity • DNA polymerase • DNA polymerase activity Cellular component • cell nucleus • nucleoplasm Biological process • DNA replication • nucleotide-excision repair • somatic hypermutation of immunoglobulin genes • cellular response to DNA damage stimulus • DNA repair • double-strand break repair via homologous recombination • base-excision repair, gap-filling • double-strand break repair via nonhomologous end joining • DNA biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	27343	56626
Ensembl	ENSG00000166169	ENSMUSG00000025218
UniProt	Q9UGP5	Q9QUG2 Q9QXE2
RefSeq (mRNA)	NM_001174084 NM_001174085 NM_001308382 NM_013274	NM_020032 NM_001330506 NM_001330507
RefSeq (protein)	NP_001167555 NP_001167556 NP_001295311 NP_037406	NP_001334531 NP_001334532 NP_001334533 NP_001334535 NP_036178 NP_001317435 NP_001317436 NP_064416
Location (UCSC)	Chr 10: 101.58 – 101.59 Mb	Chr 19: 45.55 – 45.56 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

DNA polymerase lambda, also known as POLL, is a protein found in eukaryotes. In humans, it is encoded by the POLLA gene.^[5][6]

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 (NHEJ), a pathway of DNA double-strand break (DSB) repair.^[7][8] NHEJ is the main pathway in higher eukaryotes for repair of DNA DSBs. Chromosomal DSBs are the most severe type of DNA damage. During NHEJ, duplexes generated by the alignment of broken DNA ends usually contain small gaps that need to be filled in by a DNA polymerase. DNA polymerase lambda can perform this function.^[9]

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.^[10]

In addition to NHEJ, pol λ can also participate in base excision repair (BER), where it provides backup activity in the absence of Pol β.^[11][12] BER is the major pathway for repair of small base damages resulting from alkylation, oxidation, depurination/depyrimidination, and deamination of DNA.

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.^[13] The BRCT domain is a phosphopeptide binding domain that is common among DNA repair proteins and is likely involved in coordinating protein-protein interactions.^[14] Pol λ is structurally and functionally related to pol μ, another member of the X family that also participates in non-homologous end joining.^[15] 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.^[16][17] The yeast Saccharomyces cerevisiae has a single homolog of both pol λ and pol μ called Pol4.^[18]

Translesion synthesis is a damage tolerance mechanism in which specialized DNA polymerases substitute for replicative poymerases in copying across DNA damages during replication. DNA polymerase lambda appears to be involved in translesion synthesis of abasic sites and 8-oxodG damages.^[9][19]

Interactions

Pol λ has been shown to interact with PCNA.^[20]

References

1. 
   ^ ^abc GRCh38: Ensembl release 89: ENSG00000166169 - Ensembl, May 2017
   


2. 
   ^ ^abc GRCm38: Ensembl release 89: ENSMUSG00000025218 - Ensembl, May 2017
   


3. 
   ^ "Human PubMed Reference:"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"""""""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
   


4. 
   ^ "Mouse PubMed Reference:".
   


5. 
   ^ "Entrez Gene: POLL polymerase (DNA directed), lambda".
   


6. 
   ^ 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.
   


7. 
   ^ 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.
   


8. 
   ^ 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.
   


9. 
   ^ ^ab Bebenek K, Pedersen LC, Kunkel TA (2014). "Structure-function studies of DNA polymerase λ". Biochemistry. 53 (17): 2781–92. doi:10.1021/bi4017236. PMC 4018081. PMID 24716527.
   


10. 
    ^ 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.
    


11. 
    ^ 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.
    


12. 
    ^ 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.
    


13. 
    ^ 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.
    


14. 
    ^ 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.
    


15. 
    ^ 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.
    


16. 
    ^ 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.
    


17. 
    ^ 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.
    


18. 
    ^ 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.
    


19. 
    ^ Burak MJ, Guja KE, Hambardjieva E, Derkunt B, Garcia-Diaz M (2016). "A fidelity mechanism in DNA polymerase lambda promotes error-free bypass of 8-oxo-dG". EMBO J. 35 (18): 2045–59. doi:10.15252/embj.201694332. PMC 5282837. PMID 27481934.
    


20. 
    ^ 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.
    

v t e PDB gallery

1nzp: Solution Structure of the Lyase Domain of Human DNA Polymerase Lambda 1rzt: Crystal structure of DNA polymerase lambda complexed with a two nucleotide gap DNA molecule 1xsl: Crystal Structure of human DNA polymerase lambda in complex with a one nucleotide DNA gap 1xsn: Crystal Structure of human DNA polymerase lambda in complex with a one nucleotide DNA gap and ddTTP 1xsp: Crystal Structure of human DNA polymerase lambda in complex with nicked DNA and pyrophosphate 2bcq: DNA polymerase lambda in complex with a DNA duplex containing an unpaired Dtmp 2bcr: DNA polymerase lambda in complex with a DNA duplex containing an unpaired Damp 2bcs: DNA polymerase lambda in complex with a DNA duplex containing an unpaired Dcmp 2bcu: DNA polymerase lambda in complex with a DNA duplex containing an unpaired Damp and a T:T mismatch 2bcv: DNA polymerase lambda in complex with Dttp and a DNA duplex containing an unpaired Dtmp 2gws: Crystal Structure of human DNA Polymerase lambda with a G/G mismatch in the primer terminus 2pfn: Na in the active site of DNA Polymerase lambda 2pfo: DNA Polymerase lambda in complex with DNA and dUPNPP 2pfp: DNA Polymerase lambda in complex with DNA and dCTP 2pfq: Manganese promotes catalysis in a DNA polymerase lambda-DNA crystal

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