Usage Information

Surviving without BRCA2: MLH1 gets R-looped in to curtail genomic instability
Neil Johnson
Neil Johnson
Published April 1, 2024
Citation Information: J Clin Invest. 2024;134(7):e179325. https://doi.org/10.1172/JCI179325.
View: Text | PDF
Commentary

Surviving without BRCA2: MLH1 gets R-looped in to curtail genomic instability

Abstract

While breast cancer 2 (BRCA2) loss of heterozygosity (LOH) promotes cancer initiation, it can also induce death in nontransformed cells. In contrast, mismatch repair gene mutL homolog 1 (MLH1) is a tumor-suppressor gene that protects cells from cancer development through repairing mismatched base pairs during DNA mismatch repair (MMR). Sengodan et al., in this issue of the JCI, reveal an interplay between the 2 genes: MLH1 promoted the survival of BRCA2-deficient cells independently of its MMR function. MLH1 protected replication forks from degradation, while also resolving R-loops, thereby reducing genomic instability. Moreover, MLH1 expression was regulated directly by estrogen, shedding light into the hormone-responsive nature of many BRCA2 mutant breast cancers. These results provide important insight into the genetics that drive the initiation of BRCA2-mutated breast cancers.

Authors

Neil Johnson

×

Usage data is cumulative from April 2024 through April 2025.

Usage JCI PMC
Text version 1,999 178
PDF 571 82
Figure 366 0
Citation downloads 112 0
Totals 3,048 260
Total Views 3,308

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement