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 (BER), where it provides backup activity in the absence of Pol β. 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. 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 vertebrateimmune 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.
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.
^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. PMID15964833. doi:10.1074/jbc.M505277200.
^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. PMID14561766. doi:10.1074/jbc.M307913200.
^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. PMID14992725. doi:10.1016/S1097-2765(04)00061-9.
^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. PMID15749700. doi:10.1074/jbc.M411864200.
^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. PMID11457865. doi:10.1074/jbc.M106336200.
^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. PMID15242403. doi:10.1111/j.0105-2896.2004.00160.x.
^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. PMID12932354. doi:10.1016/S1074-7613(03)00203-6.
^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. PMID16860755. doi:10.1016/j.immuni.2006.04.013.
^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. PMID27481934. doi:10.15252/embj.201694332.
^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. PMID12368291. doi:10.1074/jbc.M206889200.