To: Dr.

Musselman
From: Isabella Zhang
Subject: Peer Review for Danielle Hawryluk
Date: 11/3/17

Summary
The circadian rhythm regulates many of our homeostatic processes including sleep, body
temperature, feeding, and heart rate. The circadian rhythm is most commonly entrained to the
light-dark cycle which results from the Earths rotation on its axis. Many processes are regulated
with our circadian rhythm and when this internal clock is disrupted, it can disrupt our normal
biological processes and increase risk for disease. One risk is the potential link between
melanoma and the effects of feeding on the circadian clock. Deregulation of the circadian clock
can potentially lead to deregulation of control of the cell cycle.
Major Points
The introduction does a good job in explaining what a Zeitgber is and provides an informative
explanation of circadian rhythms. The different proteins associated with the internal clock are
introduced and related together well. The second paragraph of the introduction is much shorter,
but seems to start to get into the relationship of restricted feeding, circadian disruption and the
relationship to the development of cancer.
The title mentions restricted feeling and melanoma development, but there is not very much of
that mentioned in the review so far. Most of the review seems to focus on the mechanisms of the
clock instead of restricted feeding and its effects on melanoma which is important for
background information to understanding the mechanisms of the human clock and how it has an
effect on cancer, but the link between restricted feeding on disrupting the rhythm and how it ties
back to cancer is not heavily discussed.
In the BMAL1/CLOCK section, if there is more of a relationship between NPAS2 and how it
can relate to cancer or melanoma, perhaps the author could elaborate more about it to tie it back
to the main purpose of the paper. The Circadian and Cell Cycle Coupling briefly touches on
feeding and melanoma, and expanding upon this would bring the paper more in line with the
title.
In the Discussion, the author mentions the escape from light hypothesis but does not cite or
explain it anywhere. The paper is clearly still in work so I am sure the author will expand on the
discussion section as the review progresses. The conclusion is in bullet points, but offers good
topics that tie back to the main purpose of the review. Perhaps the author could elaborate more
on these points as they seem to discuss more about the relationship between the circadian cycle
and cancer.
So far the review does a good job in explaining the mechanisms of the human clock, but has yet
to get into what the title of the paper suggests the review is about.
Minor Points
The capitalization and italicization of the proteins/genes of the clock are not consistent
throughout the paper.