page_title: DNA replication stress
section_title: Replication fork
hierarchical_section_title: DNA replication stress / Replication fork
caption_attribution_description: English: Excess H2A.Z can cause replication defects and genome instability in the absence of the INO80 chromatin remodeler, which facilitates the removal of H2A.Z from chromatin. Aberrant H2A.Z accumulation may alter the epigenetic landscape at sites of replication stress.&#91;1&#93;
context_page_description: DNA replication stress refers to the state of a cell whose genome is exposed to various stresses. The events that contribute to replication stress occur during DNA replication, and can result in a stalled replication fork.
  There are many events that contribute to replication stress, including:
  Misincorporation of ribonucleotides
  Unusual DNA structures
  Conflicts between replication and transcription
  Insufficiency of essential replication factors
  Common fragile sites
  Overexpression or constitutive activation of oncogenes
  Chromatin inaccessibility
  ATM and ATR are proteins that help to alleviate replication stress. Specifically, they are kinases that are recruited and activated by DNA damage. The stalled replication fork can collapse if these regulatory proteins fail to stabilize it. When this occurs, reassembly of the fork is initiated in order to repair the damaged DNA end.
context_section_description: The replication fork consists of a group of proteins that influence the activity of DNA replication. In order for the replication fork to stall, the cell must possess a certain number of stalled forks and arrest length. The replication fork is specifically paused due to the stalling of helicase and polymerase activity, which are linked together. In this situation, the fork protection complex (FPC) is recruited to help maintain this linkage.
  In addition to stalling and maintaining the fork structure, protein phosphorylation can also create a signal cascade for replication restart. The protein Mrc1, which is part of the FPC, transmits the checkpoint signal by interacting with kinases throughout the cascade. When there is a loss of these kinases (from replication stress), an excess of ssDNA is produced, which is necessary for the restarting of replication.
caption: INO80 stabilizes replication forks and counteracts mislocalization of H2A.Z
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