UNASSIGNED: DNA has the ability to form a variety of secondary structures in addition to the normal B-DNA form, including hairpins and quadruplexes. These structures are implicated in a number of @entity16 and @entity5 . Expansion of a GGGGCC repeat located at @entity3301 is associated with @entity7104 ( @entity746 ) and @entity4943 ( @entity4943 ). This repeat expands from 2-24 copies in normal individuals to several hundreds or thousands of repeats in individuals with the disease. Biochemical studies demonstrated that as little as four repeats have the ability to form a stable DNA secondary structure known as a G-quadruplex. Quadruplex structures have the ability to disrupt normal DNA processes, such as DNA replication and transcription. Here, we examine the role of GGGGCC repeat length and orientation on DNA replication using an SV40 replication system in @entity1 cells. Replication through GGGGCC repeats leads to a decrease in overall replication efficiency and an increase in instability in a length-dependent manner. Both repeat expansions and contractions are observed, and replication orientation is found to influence the propensity for expansions or contractions. The presence of replication stress, such as low-dose @entity7091 , diminishes replication efficiency but has no effect on instability. Two-dimensional gel electrophoresis analysis demonstrates a replication stall with as few as 20 GGGGCC repeats. These results suggest that replication of the GGGGCC repeat at @entity3301 is perturbed by the presence of expanded repeats, which has the potential to result in further expansion, leading to disease.

DNA replication dynamics of the GGGGCC repeat of XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity16 :: ('MESH:D009422', 'Disease') :: ['neurological diseases'] @entity7091 :: ('MESH:D016590', 'Chemical') :: ['aphidicolin'] @entity3301 :: ('203228', 'Gene') :: ['C9orf72'] @entity746 :: ('MESH:D000690', 'Disease') :: ['ALS'] @entity4943 :: ('MESH:D057180', 'Disease') :: ['FTD', 'frontotemporal dementia'] @entity7104 :: ('MESH:C531617', 'Disease') :: ['familial amyotrophic lateral sclerosis']
@entity3301 :: (203228,Gene) :: ['C9orf72']
