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Direct Restart of a Replication Fork Stalled by a Head-On RNA Polymerase
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Dynamic changes in ORC localization and replication fork progression during tissue differentiation.

Brian L Hua1,2,3, George W Bell1, Helena Kashevsky1

  • 1Whitehead Institute for Biomedical Research, Cambridge, MA, 02142, USA.

BMC Genomics
|August 24, 2018
PubMed
Summary
This summary is machine-generated.

Replication repression in Drosophila is not solely due to lack of origins. Impeding DNA replication fork progression, rather than origin inhibition, controls replication in regions lacking the Origin Recognition Complex (ORC).

Keywords:
Common fragile sitesDNA replicationDrosophilaTranscription

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Genomic regions with repressed DNA replication are typically thought to be controlled by inhibiting replication origin activation.
  • However, studies in Drosophila polytene cells suggest that impeding replication fork progression may also play a significant role.

Purpose of the Study:

  • To investigate the mechanisms of replication repression in Drosophila polytene cells, focusing on tissue-specific underreplicated regions (URs).
  • To determine the role of Origin Recognition Complex (ORC) binding and replication fork progression in controlling DNA replication.

Main Methods:

  • Localization of the Origin Recognition Complex (ORC) in the larval fat body and salivary gland of Drosophila.
  • Comparison of ORC binding patterns between different tissues and cell types (polytene vs. diploid).
  • Analysis of underreplicated (UR) regions in relation to ORC binding sites and replication fork dynamics.

Main Results:

  • ORC binding sites exhibit significant tissue specificity in Drosophila polytene cells.
  • Common genomic domains lacking ORC and origins were identified in both salivary gland and fat body tissues.
  • Replication occurred in ORC-deficient domains in some polytene tissues, indicating that ORC absence alone does not repress replication.
  • Replication of ORC-deficient regions is dependent on the inhibition of replication forks originating outside these regions.

Conclusions:

  • Inhibition of replication fork progression is a key mechanism for blocking replication in genomic regions that constitutively lack ORC.
  • Replication fork progression can be regulated in both tissue-specific and genomic region-specific manners.
  • Altered control of replication forks during differentiation is a critical factor to consider when evaluating sources of genome instability.