AI Article Synopsis
- DNA replication can get messed up when it stops or breaks, which can harm the DNA.
- Scientists found a special complex made of two proteins, MMS22L and TONSL, that helps fix these problems when they happen.
- If there’s not enough MMS22L and TONSL, cells can get a lot of DNA damage and struggle to repair themselves properly.
Article Abstract
Genome integrity is jeopardized each time DNA replication forks stall or collapse. Here we report the identification of a complex composed of MMS22L (C6ORF167) and TONSL (NFKBIL2) that participates in the recovery from replication stress. MMS22L and TONSL are homologous to yeast Mms22 and plant Tonsoku/Brushy1, respectively. MMS22L-TONSL accumulates at regions of ssDNA associated with distressed replication forks or at processed DNA breaks, and its depletion results in high levels of endogenous DNA double-strand breaks caused by an inability to complete DNA synthesis after replication fork collapse. Moreover, cells depleted of MMS22L are highly sensitive to camptothecin, a topoisomerase I poison that impairs DNA replication progression. Finally, MMS22L and TONSL are necessary for the efficient formation of RAD51 foci after DNA damage, and their depletion impairs homologous recombination. These results indicate that MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031522 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2010.10.024 | DOI Listing |
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