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Related Concept Videos

Homologous Recombination02:31

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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
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The human SRCAP chromatin remodeling complex promotes DNA-end resection.

Shunli Dong1, Jinhua Han1, Hongxia Chen1

  • 1Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China.

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|September 2, 2014
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Summary

The SRCAP chromatin remodeling complex promotes DNA double-strand break (DSB) repair by aiding CtIP-dependent resection. SRCAP

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Area of Science:

  • Molecular Biology
  • Chromatin Biology
  • DNA Repair

Background:

  • DNA double-strand breaks (DSBs) require 5'-3' resection for repair via homologous recombination.
  • CtIP and the MRN complex initiate DSB resection in vertebrates.
  • The role of chromatin in DSB resection remains unclear.

Purpose of the Study:

  • To investigate the role of the SRCAP chromatin remodeling complex in DNA double-strand break repair.
  • To elucidate the mechanism by which SRCAP influences DNA-end resection and homologous recombination.

Main Methods:

  • Identifying SRCAP as a factor in CtIP-dependent DNA-end resection.
  • Assessing SRCAP recruitment to DSBs and its effect on resection.
  • Investigating SRCAP's role in RPA and RAD51 recruitment and homologous recombination.
  • Analyzing SRCAP's interaction with CtIP and its ATPase activity.

Main Results:

  • SRCAP promotes CtIP-dependent DNA-end resection.
  • SRCAP is recruited to DSBs and confers resistance to DNA-damaging agents.
  • SRCAP is essential for DNA-end resection, RPA/RAD51 recruitment, and homologous recombination.
  • SRCAP forms a complex with CtIP, enhancing CtIP accumulation at DSBs via its ATPase activity.

Conclusions:

  • SRCAP is a novel regulator of DNA damage responses.
  • SRCAP orchestrates DNA double-strand break signaling and repair within chromatin.
  • SRCAP's function is critical for maintaining genomic stability.