Abstract
In order to pass on an intact copy of the genome during cell division, complete and faithful DNA replication is crucial. Yet, certain areas of the genome are intrinsically challenging to replicate, which manifests as high local mutation propensity. Such regions include trinucleotide repeat sequences, common chromosomal fragile sites (CFSs), and early replicating fragile sites (ERFSs). Despite their genomic instability CFSs are conserved, suggesting that they have a biological function. To shed light on the potential function of CFSs, this review summarizes the similarities and differences of the regions that challenge DNA replication with main focus on CFSs. Moreover, we review the mechanisms that operate when CFSs fail to complete replication before entry into mitosis. Finally, evolutionary perspectives and potential physiological roles of CFSs are discussed with emphasis on their potential role in neurogenesis.
Highlights
Regions that are difficult to replicate are at high risk of failing replication before cells enter mitosis, and this gives rise to microscopically visible gaps on metaphase chromosomes (Figure 1).Such regions, which are incompletely replicated in mitosis, are referred to as underreplicated.Several causes of local replication difficulties have been identified, including tandem repetitive DNA sequences, transcription activities, and timing of replication
Studies of trinucleotide repeat expansion led to the discovery of another type of regions that are difficult to replicate due to certain transcription and replication patterns
By performing quantitative reverse transcriptase PCR (RT-qPCR) on introns of chromosomal fragile sites (CFSs) genes Helmrich et al characterized the nascent expression of those genes in relation to the cell cycle phase
Summary
Regions that are difficult to replicate are at high risk of failing replication before cells enter mitosis, and this gives rise to microscopically visible gaps on metaphase chromosomes (Figure 1). Due proposed physiological role of inherently unstable short tandem DNA repeats is relatively recent, to their involvement in diseases, trinucleotide DNA repeats have been widely studied and it is clear pathological consequences ofDNA trinucleotide repeat expansions beendamage known [8]. That this type of repeat causes replication fork stallinghave and DNA short Due to their involvement in diseases, trinucleotide repeats have widely studied and it from is clear that tandem DNA repeats cause replicationDNA problems, they are been highly genetically unstable generation extensive changes in and copyDNA numbers between individuals [9].tandem this typegeneration of repeatto causes with replication fork stalling damage [8]. They have a tendency to form gaps on metaphase chromosomes in response to replication stress, which is why extensive trinucleotide repeat expansions give rise to so-called rare fragile sites that are occasionally associated with disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
