Function
of DNA Ligas

This picture shows DNA Ligase
I attached at a repair site on
double-stranded DNA (retrieved from Wikipedia)
DNA can be damaged by a number of things,
such as
ultraviolet light, radiation, oxidation agents, and alkylating agents. The primary function of DNA
Ligase is to
replicate, recombine, and repair DNA. There
are two classes of DNA Ligase: NAD-Dependent
and ATP-Dependent. Only ATP-Dependent forms of the enzyme are found in
mammalian cells. In humans, there are four distinct forms: DNA Ligases
I, II, III, and IV.
While all DNA ligases are involved in DNA repair
mechanisms, each of the four have distinct functions in various
pathways. Their structures differ slightly, leading to the binding to
different proteins and repair sites for each DNA ligase form. DNA
ligases I and III are the most abundant of the four types found in the
mammalian body. It has recently been suggested that DNA Ligase III,
not DNA Ligase I, accounts for over 85% of the joining of DNA strands
in mammalian cells.
Current research has led to following functions of
each of the common types of DNA ligases found in humans:
- DNA ligase I: This form of the enzyme joins
Okazaki fragments during lagging strand DNA replication and some
recombinant fragments. It interacts with PCNA to aid in its functions.
It is also involved in base-excision repair and nucleotide-excision
repair
- DNA ligase II: This form is
very similar to and is thought to be derived from DNA Ligase III.
However, this form of ligase is found in non-dividing cells of mammals.
(alternatively spliced form)
DNA Ligase III includes a zinc finger, which
aids in locating strand breaks needing repair. The
two forms DNA
ligase-alpha and DNA ligase-beta differ in their
c-terminal amino acid sequence. DNA
Ligase
III-alpha found in all human somatic
cells interacts with XRCC1, another DNA repair protein. DNA
Ligase III-beta,
however, is only found in the testis and does not form a
complex with XRCC1,
suggesting that its serves functions other than DNA
repair. DNA
Ligase III is involved in meiosis. It
has been suggested that this
enzyme aids in the homologous recombinations
that occur before the
first meiotic division.
- DNA Ligase IV: It
catalyzes the final step in double-strand break repair, while
interacting with the XRCC4, a double-stranded break repair protein. It
is also required for the process which generates diversity in cell loci
during immune system development. It has been suggested that DNA
ligase IV is involved in early embryonic development. This was
discovered when mice embryos were killed when the function of this
enzyme.

Information for this page was
obtained from:
Petrini, J.H., Xiao, Y., and Weaver, D.T. "DNA ligase I mediates
essential functions in mammalian cells." Molecular and Cellular
Biology. 1995. Vol
15(8). 4303-4308. Accessed from Molecular and Cellular Biology
<http://mcb.asm.org/cgi/content/abstract/15/8/4303>.
Tomkinson, A.E.,
and Mackey, Z.B. "Structure and function of mammalian DNA ligases."
Mutation Research. 1998. Vol 401(8). 1-9. Accessed
from PubMed
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9539976&
query_hl=5&itool=pubmed_docsum>.
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