Nuclear and Kinetoplast DNA Replication in Trypanosomatids
Pp. 134-194 (61)
Marcelo S. da Silva, Maria Alejandra Viviescas, Raphael Souza Pavani, Edna Gicela Ortiz, Camila B. Storti and Maria Isabel N. Cano
Trypanosomatids are among the most primitive eukaryotes and therefore
exhibit both conserved and unique non-conserved features in the DNA replication
machinery. In eukaryotes, nuclear DNA replication is preceded by the assembly of the
pre-replication complex (pre-RC), which is coordinated by the six-subunit origin
recognition complex (ORC), which together with the Cdc6 and Cdt1 proteins play a
central role in the loading of the hetero-hexamer Mcm2-7. In the domain Archaea there
are no Cdt1 protein homologs, Mcm is a homo-hexamer, which is recruited by a protein
that shows homology with ORC, and Cdc6 (called Orc/Cdc6). Curiously, trypanosomatid
pre-RC differs from others eukaryotes in this context, and it appears more
similar to that of Archaea, presenting a homolog of protein Orc/Cdc6 and no homologs
of Cdt1, in addition to present Mcm as a hetero-hexamer complex. The completion of
DNA replication, at trypanosomatid telomeres, apparently is similar to other
eukaryotes, although the processing of the leading and lagging telomeres required to
generate the 3' overhangs, which serves as telomerase substrate, remains unknown.
With the generation of overhangs at the ends of the chromosomes, telomeres are
frequently extended by the action of telomerase, whose control also remains unknown.
It is worth mentioning that DNA replication in trypanosomatids initiates almost
simultaneously in the nucleus and the kinetoplast, suggesting that regulation of DNA
synthesis in the two DNA-containing organelles may be coordinated. The kinetoplast
DNA (kDNA) consists of mini- and maxicircles, which are replicated by many proteins whose mechanisms of action remain unclear. This chapter aims to review and discuss
the complex DNA replication mechanisms that act independently in the kinetoplast and
the nucleus, as well as some fascinating peculiarities exclusive to trypanosomatids
DNA polymerases, Kinetoplast DNA replication, Nuclear DNA
replication, Origin Firing, Origin Licensing, Origin recognition complex,
Replication forks, Replisome, Telomere replication, Topoisomerases.
Genetics Departament - IB, São Paulo State University “Júlio de Mesquita Filho” (UNESP), Botucatu, São Paulo, Brazil.