BRIT1/MCPH1 links chromatin remodelling to DNA damage response.

ABSTRACT: To detect and repair damaged DNA, DNA-damage-response proteins need to overcome the barrier of condensed chromatin to gain access to DNA lesions. ATP-dependent chromatin remodelling is one of the fundamental mechanisms used by cells to relax chromatin in DNA repair. However, the mechanism mediating their recruitment to DNA lesions remains largely unknown. BRIT1 (also known as MCPH1) is an early DNA-damage-response protein that is mutated in human primary microcephaly. Here we report a previously unknown function of BRIT1 as a regulator of the ATP-dependent chromatin remodelling complex SWI-SNF in DNA repair. After damage to DNA, BRIT1 increases its interaction with SWI-SNF through ATM/ATR-dependent phosphorylation on the BAF170 subunit. This increase in binding affinity provides a means by

SUBMITTER: Peng G 

PROVIDER: S-EPMC2714531 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature