Dataset Information

Mind the replication gap.

ABSTRACT: Unlike bacteria, mammalian cells need to complete DNA replication before segregating their chromosomes for the maintenance of genome integrity. Thus, cells have evolved efficient pathways to restore stalled and/or collapsed replication forks during S-phase, and when necessary, also to delay cell cycle progression to ensure replication completion. However, strong evidence shows that cells can proceed to mitosis with incompletely replicated DNA when under mild replication stress (RS) conditions. Consequently, the incompletely replicated genomic gaps form, predominantly at common fragile site regions, where the converging fork-like DNA structures accumulate. These branched structures pose a severe threat to the faithful disjunction of chromosomes as they physically interlink the partially duplicated sister chromatids. In this review, we provide an overview discussing how cells respond and deal with the under-replicated DNA structures that escape from the S/G2 surveillance system. We also focus on recent research of a mitotic break-induced replication pathway (also known as mitotic DNA repair synthesis), which has been proposed to operate during prophase in an attempt to finish DNA synthesis at the under-replicated genomic regions. Finally, we discuss recent data on how mild RS may cause chromosome instability and mutations that accelerate cancer genome evolution.

SUBMITTER: Mocanu C

PROVIDER: S-EPMC8188003 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PurposeMedical students may take a year off during medical school (a "gap year") to strengthen their applications for competitive specialties such as radiation oncology. This can incur significant financial and opportunity costs. We sought to understand the prevalence, nature, and funding of gap years undertaken by radiation oncology applicants.Methods and materialsAn anonymous survey was emailed to all applicants to a single radiation oncology program from 2015 to 2017. Survey questions assessed gap year utilization, funding, motivations, and perceptions. Separately, all 2017 Electronic Residency Application Service (n = 176) applications to this program were reviewed for reference.ResultsThe 2017 cohort had a response rate of 69% (n = 121), with an overall response rate of 39% (n = 194) for applicants between 2015 to 2017. Of non-MD/PhD respondents, 33% (n = 53) reported taking a gap year. The main reason for a gap year (68%) was to produce more publications, and 50% of all respondents viewed a gap year as "important" or "very important" for matching in radiation oncology. Twenty-eight students (53%) reported using personal loans, savings, or family support to cover gap year expenses. Most who took a gap year (83%) viewed funding as "difficult" or "extremely difficult" to obtain. Fewer publications before gap year and more dedicated research time were significant predictors of undertaking a gap year, whereas sex, marital status, dependent status, and financial aid were not significant.ConclusionsResearch productivity is commonly perceived as important for matching in radiation oncology, leading many applicants to take gap years, which are usually supported by personal financial resources. We did not identify statistically significant socioeconomic disparities between applicants that took a gap year and those who did not. However, further study is warranted to determine whether pressure to take a gap year, particularly in the absence of readily available funding sources, deters some potential applicants from pursuing radiation oncology altogether.

Dataset Information

Mind the replication gap.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets