Repair Scaffolding Reaches New Heights at Blocked Replication Forks

Abstract

In this issue of Molecular Cell, Ohouo et al. (2010) show that Mec1 (hATR) promotes the association of Slx4 and Rtt107 with Dpb11 (hTopBP1) in response to MMS-induced DNA alkylation, suggesting that Slx4 and Rtt107 might coordinate repair factors specifically at damaged replication forks.

Structure of C-terminal Tandem BRCT Repeats of Rtt107 Protein Reveals Critical Role in Interaction with Phosphorylated Histone H2A during DNA Damage Repair

“…There are three pairs of BRCT repeats in Rtt107. It is believed that Rtt107 may act as a scaffold during DNA damage repair (17,19,46). In support of this hypothesis, Rtt107 was found to interact with various factors and enzymes involved in the DNA damage response, such as Slx4, Rad55, Rtt101, and Smc5/6.…”

SLX4: multitasking to maintain genome stability

“…DAMP relies on the simultaneous interaction of Rtt107 with SLX4 and H2A phosphorylated by Mec1 ((γH2A), via its N-terminus (BRCT1-4) and its last two BRCT domains 5 and 6, respectively (Zappulla et al 2006;Roberts et al 2006;Li et al 2012;Ohouo et al 2013). It also relies on the binding by Dpb11 to SLX4 phosphorylated by CDK at serine S486 and by Mec1 at SQ/TQ sites (Downey et al 2010;Ohouo et al 2010;Gritenaite et al 2014). This Dpb11-Slx4 interaction relies on the BRCT domains 1 and 2 of Dpb11 which also mediate interaction with phosphorylated Rad9 (Pfander & Diffley 2011).…”