Small World Biology

How Cells Do What They Do

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The story behind this site.

I've always been amazed at life at the cellular level. Inside every one of your 50 trillion or so cells, untold quintillions of molecular machines are performing complex tasks with incredible precision. Yet nobody is running the show. Everything that takes place there--in fact, life itself--arises spontaneously from inanimate matter randomly crashing around. How can precision arise from randomness?

In this blog I try to paint a very detailed picture of the cellular world for non-scientists that underscores this seeming contradiction. I'll be presenting the cell's activities at a deeper level than is typically presented to a general audience. The content of this blog will often be at or above the level of a graduate school course.

In order to go deep, though, we can't go too wide. So, after covering some foundational molecular biology, our focus will be on just one of the cell's activities: the process by which it copies, or replicates, its genome with high accuracy prior to cell division. It's a massive task, and the steps the cell goes through to accomplish it are mind boggling.

Enjoy! And please share your thoughts. I'd like to get better at writing about this topic so I appreciate your feedback.

DNA Lesions IV

Global Response In addition to the local response to a lesion initiated by phosphorylated CHK1 (that is, fork stabilization in the form of fork protection and potentially fork reversal) the presence of high levels of phosphorylated CHK1 also contribute to a call for a global, cell-wide response. The cell-wide response takes the form of cell cycle arrest at the intra-S-phase checkpoint. This buys time for the cell to address what now appears to be (based on very high levels o

lscole

DNA Lesions III

In the last post, we learned about fork protection , a mode cells enter when a lesion stalls at a polymerase. Its purpose is to stabilize the replisome's structure and protect exposed DNA, affording the cell time to deal with the fork-stalling lesion. Fork protection is part of a larger process that's usually referred to as fork stabilization. It has two parts. It starts with fork protection, which unfolds in minutes to tens of minutes after the detection of RPA-dsDNA. At th

lscole

DNA Lesions II

In the last post, I introduced the cell's two main DNA lesion repair pathways-- base excision repair (BER) and nucleotide excision repair (NER) . Both operate well beyond the replication fork during all of the phases of the cell cycle. But what happens if a lesion escapes BER and NER and finds itself in S phase in front of a moving replication fork? Most DNA lesions get past the CMG helicase but not the DNA polymerase, although some very large lesions can't get past the heli

lscole