AI Article Synopsis
- DNA repair for double-stranded breaks involves creating single-stranded DNA ends through a process called DNA end resection.
- Researchers reconstituted this process using specific human proteins, including Bloom helicase (BLM), DNA2, EXO1, and the MRN complex (MRE11, RAD50, NBS1), along with RPA.
- There are two main pathways for hairpin resection: one relies on the interaction between BLM and DNA2 with ATP dependence, while the other utilizes EXO1, which is supported by BLM and MRN to enhance its activity and affinity for DNA ends.
- This study defines key mechanisms and proteins involved in initiating recombinational DNA repair in human cells.
Article Abstract
Repair of dsDNA breaks requires processing to produce 3'-terminated ssDNA. We biochemically reconstituted DNA end resection using purified human proteins: Bloom helicase (BLM); DNA2 helicase/nuclease; Exonuclease 1 (EXO1); the complex comprising MRE11, RAD50, and NBS1 (MRN); and Replication protein A (RPA). Resection occurs via two routes. In one, BLM and DNA2 physically and specifically interact to resect DNA in a process that is ATP-dependent and requires BLM helicase and DNA2 nuclease functions. RPA is essential for both DNA unwinding by BLM and enforcing 5' → 3' resection polarity by DNA2. MRN accelerates processing by recruiting BLM to the end. In the other, EXO1 resects the DNA and is stimulated by BLM, MRN, and RPA. BLM increases the affinity of EXO1 for ends, and MRN recruits and enhances the processivity of EXO1. Our results establish two of the core machineries that initiate recombinational DNA repair in human cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042158 | PMC |
| http://dx.doi.org/10.1101/gad.2003811 | DOI Listing |
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