ISSN:
1573-6768
Schlagwort(e):
accessory protein
;
aging
;
DNA polymerase α
;
DNA synthesis
;
SV40 T antigen
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
Abstract During the past decade intense investigation hasfocused on cellular aging with the expectation ofdiscovering factors that regulate the replicationcomplex and contribute to the onset and progression ofcellular aging. The most striking feature of cellular aging is the failure of senescing diploidcells to enter or complete S phase of the cellcycle. The G1/S phase transition is an initialcritical step in the regulation of proliferation ineukaryotic cells, and significant advances have beenmade toward understanding the basic mechanisms ofaging by identifying components of the macromolecularassemblies participating in the G1/S transition. These studies have identified multiple DNA polymerasesand their accessory factors, and have providedimportant strategies for investigating the molecularevents that contribute to aging processes. DNAreplication, repair and recombination in eukaryoticcells require the action of a variety of DNApolymerases, at least six of which are known,α, β, γ, δ, ∈, andζ. Among them the highly conserved DNApolymerase α-primase (pol α-primase) isthe only enzyme capable of initiating DNA replicationat chromosomal origin sites and at sites of initiationof discontinuous synthesis of Okazaki fragments on thelagging side of the replication fork. Numerousprotein factors that play strategic roles in DNAreplication have been identified and the understandingof their regulation has been an important step foridentifying the elements that are involved in, andpossibly necessary for, governing cellular senescenceand aging. In this review we summarize the current informationregarding DNA pol α modulation during aging. We focus in particular on the coordinated actions of DNA pol α in the presence of other cellularproteins involved in the replication complex in thehope that understanding pol α interactions withcomponents of the replication complex may provideinsight into the mechanisms by which aging andage-related diseases occur.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1023/A:1010084706732
Permalink
