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Preferential re-replication of Drosophila heterochromatin in the absence of geminin.

Publication ,  Journal Article
Ding, Q; MacAlpine, DM
Published in: PLoS genetics
September 2010

To ensure genomic integrity, the genome must be duplicated exactly once per cell cycle. Disruption of replication licensing mechanisms may lead to re-replication and genomic instability. Cdt1, also known as Double-parked (Dup) in Drosophila, is a key regulator of the assembly of the pre-replicative complex (pre-RC) and its activity is strictly limited to G1 by multiple mechanisms including Cul4-Ddb1 mediated proteolysis and inhibition by geminin. We assayed the genomic consequences of disregulating the replication licensing mechanisms by RNAi depletion of geminin. We found that not all origins of replication were sensitive to geminin depletion and that heterochromatic sequences were preferentially re-replicated in the absence of licensing mechanisms. The preferential re-activation of heterochromatic origins of replication was unexpected because these are typically the last sequences to be duplicated in a normal cell cycle. We found that the re-replication of heterochromatin was regulated not at the level of pre-RC activation, but rather by the formation of the pre-RC. Unlike the global assembly of the pre-RC that occurs throughout the genome in G1, in the absence of geminin, limited pre-RC assembly was restricted to the heterochromatin by elevated cyclin A-CDK activity. These results suggest that there are chromatin and cell cycle specific controls that regulate the re-assembly of the pre-RC outside of G1.

Duke Scholars

Published In

PLoS genetics

DOI

EISSN

1553-7404

ISSN

1553-7390

Publication Date

September 2010

Volume

6

Issue

9

Start / End Page

e1001112

Related Subject Headings

  • Ploidies
  • Heterochromatin
  • Geminin
  • Drosophila melanogaster
  • Drosophila Proteins
  • Developmental Biology
  • DNA Replication Timing
  • DNA Replication
  • Cyclin-Dependent Kinases
  • Cyclin A
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ding, Q., & MacAlpine, D. M. (2010). Preferential re-replication of Drosophila heterochromatin in the absence of geminin. PLoS Genetics, 6(9), e1001112. https://doi.org/10.1371/journal.pgen.1001112
Ding, Queying, and David M. MacAlpine. “Preferential re-replication of Drosophila heterochromatin in the absence of geminin.PLoS Genetics 6, no. 9 (September 2010): e1001112. https://doi.org/10.1371/journal.pgen.1001112.
Ding Q, MacAlpine DM. Preferential re-replication of Drosophila heterochromatin in the absence of geminin. PLoS genetics. 2010 Sep;6(9):e1001112.
Ding, Queying, and David M. MacAlpine. “Preferential re-replication of Drosophila heterochromatin in the absence of geminin.PLoS Genetics, vol. 6, no. 9, Sept. 2010, p. e1001112. Epmc, doi:10.1371/journal.pgen.1001112.
Ding Q, MacAlpine DM. Preferential re-replication of Drosophila heterochromatin in the absence of geminin. PLoS genetics. 2010 Sep;6(9):e1001112.

Published In

PLoS genetics

DOI

EISSN

1553-7404

ISSN

1553-7390

Publication Date

September 2010

Volume

6

Issue

9

Start / End Page

e1001112

Related Subject Headings

  • Ploidies
  • Heterochromatin
  • Geminin
  • Drosophila melanogaster
  • Drosophila Proteins
  • Developmental Biology
  • DNA Replication Timing
  • DNA Replication
  • Cyclin-Dependent Kinases
  • Cyclin A