DNA polymerase lambda, a novel DNA repair enzyme in human cells.
DNA polymerase lambda (pol lambda) is a novel family X DNA polymerase that has been suggested to play a role in meiotic recombination and DNA repair. The recent demonstration of an intrinsic 5'-deoxyribose-5-phosphate lyase activity in pol lambda supports a function of this enzyme in base excision repair. However, the biochemical properties of the polymerization activity of this enzyme are still largely unknown. We have cloned and purified human pol lambda to homogeneity in a soluble and active form, and we present here a biochemical description of its polymerization features. In support of a role in DNA repair, pol lambda inserts nucleotides in a DNA template-dependent manner and is processive in small gaps containing a 5'-phosphate group. These properties, together with its nucleotide insertion fidelity parameters and lack of proofreading activity, indicate that pol lambda is a novel beta-like DNA polymerase. However, the high affinity of pol lambda for dNTPs (37-fold over pol beta) is consistent with its possible involvement in DNA transactions occurring under low cellular levels of dNTPs. This suggests that, despite their similarities, pol beta and pol lambda have nonredundant in vivo functions.
García-Díaz
Miguel
M
Centro de Biologia Molecular Severo Ochoa (CSIC-UAM), Universidad Autónoma, Cantoblanco, Madrid 28049, Spain.
Bebenek
Katarzyna
K
Sabariegos
Rosario
R
Domínguez
Orlando
O
Rodríguez
Josana
J
Kirchhoff
Tomas
T
García-Palomero
Esther
E
Picher
Angel J
AJ
Juárez
Raquel
R
Ruiz
Jose F
JF
Kunkel
Thomas A
TA
Blanco
Luis
L
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D019951:DNA Polymerase beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D004260:DNA Repair; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D018076:DNA, Complementary; C415367:DNA polymerase beta2; D019951:DNA Polymerase beta