Purinosome formation as a function of the cell cycle.

Proc Natl Acad Sci U S A
Authors
Keywords
Abstract

The de novo purine biosynthetic pathway relies on six enzymes to catalyze the conversion of phosphoribosylpyrophosphate to inosine 5'-monophosphate. Under purine-depleted conditions, these enzymes form a multienzyme complex known as the purinosome. Previous studies have revealed the spatial organization and importance of the purinosome within mammalian cancer cells. In this study, time-lapse fluorescence microscopy was used to investigate the cell cycle dependency on purinosome formation in two cell models. Results in HeLa cells under purine-depleted conditions demonstrated a significantly higher number of cells with purinosomes in the G1 phase, which was further confirmed by cell synchronization. HGPRT-deficient fibroblast cells also exhibited the greatest purinosome formation in the G1 phase; however, elevated levels of purinosomes were also observed in the S and G2/M phases. The observed variation in cell cycle-dependent purinosome formation between the two cell models tested can be attributed to differences in purine biosynthetic mechanisms. Our results demonstrate that purinosome formation is closely related to the cell cycle.

Year of Publication
2015
Journal
Proc Natl Acad Sci U S A
Volume
112
Issue
5
Pages
1368-73
Date Published
2015 Feb 03
ISSN
1091-6490
URL
DOI
10.1073/pnas.1423009112
PubMed ID
25605889
PubMed Central ID
PMC4321313
Links
Grant list
R01 GM024129 / GM / NIGMS NIH HHS / United States
R37 GM024129 / GM / NIGMS NIH HHS / United States
GM024129 / GM / NIGMS NIH HHS / United States