Mus81/Mms4 nuclease and cleavage of replication/recombination intermediates
| Title in English | HHMI Meeting of International Research Scholars |
|---|---|
| Authors | |
| Year of publication | 2008 |
| Type | R&D Presentation |
| MU Faculty or unit | |
| Citation | |
| Description | DNA replication is typically highly processive mechanism with astonishing precision, despite the fact that it frequently encounters barriers caused by endogenous and exogenous genotoxic agents. It is not surprising that DNA replication does not act alone, but operate in coordination with recombination, and DNA repair processes to overcame such replication obstacles, ensure cellular viability and achieve genomic stability. Several mechanisms by which replication forks can be restarted following arrest have been described with Mus81/Mms4 complex, possessing structure specific endonuclease activity, being one of them. The mus81 mutant shows synthetic interaction with mutations in replication proteins and hypersensitivity genotoxic reagents that in general cause replication fork stalling and collapse. In addition, Mus81 is also known to play role in normal processing of DNA lesion and its inactivation result in elevated levels of genomic instability, elicits checkpoint activation and checkpoint-dependent cell cycle arrest. Our study shows direct association between Rad54 and Mus81 using purified proteins as well as dramatic stimulation of Mus81/Mms4 activity by Rad54 protein on variety of substrates. In addition, we provide evidence that ATP binding and hydrolysis is not required for this stimulation and Rad54 is able to target Mus81/Mms4 complex to its substrates. We propose that Rad54 together with Mus81/Mms4 protein is involved in processing DNA substrates that are intermediates arising during DNA replication and recombination. |
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