MAMMALIAN DNA LIGASES

DNA joining enzymes play an essential role in the maintenance of genom ic integrity and stability. Three mammalian genes encoding DNA ligases , LIG1, LIG3 and LIG4, have been identified. Since DNA ligase II appea rs to be derived from DNA ligase III by a proteolytic mechanism, the t hree LIG genes can account for the four biochemically distinct DNA lig ase activities, DNA ligases I, II, III and IV, that have been purified from mammalian cell extracts. It is probable that the specific cellul ar roles of these enzymes are determined by the proteins with which th ey interact. The specific involvement of DNA ligase I in DNA replicati on is mediated by the non-catalytic amino-terminal domain of this enzy me. Furthermore, DNA ligase I participates in DNA base excision repair as a component of a multiprotein complex. Two forms of DNA ligase III are produced by an alternative splicing mechanism. The ubiqitously ex pressed DNA ligase III-alpha forms a complex with the DNA single-stran d break repair protein XRCC1. In contrast, DNA ligase III-beta, which does not interact with XRCC1, is only expressed in male meiotic germ c ells, suggesting a role for this isoform in meiotic recombination. At present, there is very little information about the cellular functions of DNA ligase IV.